Female gender is associated with a better outcome after cardiac resynchronization therapy

Background: Some studies have suggested that women respond differently to cardiac resynchronization therapy (CRT). We sought to determine whether female gender influences long‐term clinical outcome, symptomatic response as well as echocardiographic response after CRT. Methods and Results: A total of 550 patients (age 70.4 ± 10.7 yrs [mean ± standard deviation]) were followed up for a maximum of 9.1 years (median: 36.2 months) after CRT‐pacing (CRT‐P) or CRT‐defibrillation (CRT‐D) device implantation. Outcome measure included mortality as well as unplanned hospitalizations for heart failure or major adverse cardiovascular events (MACE). Female gender predicted survival from cardiovascular death (hazard ratio [HR]: 0.52, P = 0.0051), death from any cause (HR: 0.52, P = 0.0022), the composite endpoints of cardiovascular death /heart failure hospitalizations (HR: 0.56, P = 0.0036) and death from any cause/hospitalizations for MACE (HR: 0.67, P = 0.0214). Female gender predicted death from pump failure (HR: 0.55, P = 0.0330) but not sudden cardiac death. Amongst the 322 patients with follow‐up echocardiography, left ventricular (LV) reverse remodelling (≥15% reduction in LV end‐systolic volume) was more pronounced in women (62% vs 44%, P = 0.0051). In multivariable Cox proportional hazards analyses, the association between female gender and cardiovascular survival was independent of age, LV ejection fraction, atrial rhythm, QRS duration, CRT device type, New York Heart Association (NYHA) class, and LV reverse remodelling (adjusted HR: 0.48, P = 0.0086). At one year, the symptomatic response rate (improvement by ≥1 NYHA classes or ≥25% increase in walking distance) was 78% for both women and men. Conclusions: Female gender is independently associated with a lower mortality and morbidity after CRT. (PACE 2011; 82–88)     

Assessing reverse remodeling in heart failure patients treated with cardiac resynchronization therapy and its impact on prognosis

Cardiac resynchronization therapy (CRT) has become an alternative for patients with systolic dysfunction and persistence of heart failure symptoms despite optimal medical therapy. The role of noninvasive cardiac imaging before device implantation still remains controversial, but they are essential to provide an objective evidence of reverse remodeling of the heart which is, in turn, also related to the outcome of patients treated with CRT. The objective of this review is to highlight the acute and long-term CRT benefits as assessed by imaging, with special focus in cardiac reverse remodeling and its impact on prognosis.     

QRS duration and shortening to predict clinical response to cardiac resynchronization therapy in patients with end-stage heart failure

Despite current selection criteria (NYHA Class III-IV, LVEF < 35%, QRS > 120 ms with LBBB), 30% of patients do not benefit from cardiac resynchronization therapy (CRT). The use of QRS duration as selection criteria for CRT has not been evaluated systematically yet. Accordingly, the value of QRS duration at baseline (and reduction in QRS duration after CRT) to predict responders was studied. Patients were evaluated at baseline and after 6 months of CRT for NYHA Class, quality of life score, and 6-minute walk test. QRS duration was evaluated before, directly after implantation, and after 6 months of CRT. Sixty-one patients were included; 45 (74%) patients were classified as responders (improvement of NYHA Class, 6-minute walking distance and quality of life score) and 16 (26%) as nonresponders. QRS duration at baseline was similar between the two groups: 179 +/- 30 ms versus 171 +/- 32 ms, NS. Directly after implantation, QRS duration was reduced from 179 +/- 30 ms to 150 +/- 26 ms (P < 0.01) in responders; nonresponders did not exhibit this reduction (171 +/- 32 ms vs 160 +/- 26 ms, NS). After 6 months of CRT, QRS shortening was only observed in responders (from 179 +/- 30 ms to 159 +/- 25 ms, P < 0.01). ROC curve analysis showed that a reduction in QRS duration > 10 ms had a high sensitivity (73%) with low specificity (44%); conversely, a > 50 ms reduction in QRS duration was highly specific (88%) but not sensitive (18%) to predict response to CRT. No optimal cutoff value could be defined. QRS duration at baseline is not predictive for response to CRT; responders exhibit a significant reduction in QRS duration after CRT, but individual response varies highly, not allowing adequate selection of responders.     

Relationship of baseline electrocardiographic characteristics with the response to cardiac resynchronization therapy for heart failure

Prospective identification of patients most and least likely to respond to cardiac resynchronization therapy (CRT) for congestive heart failure (CHF) will allow clinicians to target this intervention most efficiently. The authors hypothesized that ECG variables including RBBB and indicators of RV dysfunction and extensive prior myocardial infarction would correlate with diminished response to CRT. This study analyzed preimplantation ECGs in 110 patients with ICD indications and CHF due to left ventricular systolic dysfunction randomized to active biventricular pacing in the MIRACLE ICD trial. Clinical and ECG variables on the outcome of change in peak oxygen consumption from baseline to 6 months (Delta-VO2 ) were evaluated. For this cohort, average peak VO2 improved from 13.4 to 14.3 mL/kg per minute. Among clinical variables, the strongest predictors of increasing Delta-VO2 were reduced exercise time and peak VO2 at baseline. A dominant R wave in lead a VR, RBBB, and evidence of prior anterior infarction were each associated with significantly smaller average improvements in Delta-VO2 than their absence in univariate analysis. Alternative ECG criteria, including QRS duration, had no relationship with the outcome. In a multivariate model, only baseline VO2 (beta=-0.3, P=0.001) and ECG evidence of prior anterior infarction (beta=-1.3, P=0.03) were associated with the outcome. ECG markers of anterior infarction and RV dilation may help identify CHF patients unlikely to benefit from biventricular pacing. Further assessment is needed of these and other predictors of therapeutic response to CRT.     

Left ventricular dysfunction after cardiac resynchronization therapy in congenital heart disease patients with a failing systemic right ventricle

Background: Cardiac resynchronization therapy is rapidly emerging as an effective strategy for managing ventricular dysfunction and heart failure associated with congenital heart disease. Indications for therapy, optimal lead placement, and late outcomes are however lacking.
Methods: We present three patients, one with Mustard procedure and two with congenitally corrected transposition of great arteries, who developed subpulmonic ventricular dysfunction 3–6 months after biventricular pacing ± implantable cardioverter defibrillator implantation, despite initial favorable result of resynchronization therapy. Possible factors for adverse outcome are relatively high pacing rate, unfavorable alteration of torsional contraction, and increased atrioventricular valve regurgitation due to suboptimal placement of larger diameter defibrillation leads.
Results: Careful evaluation of patients, particularly indications for therapy, need to be rigorous; assessment of hemodynamic response at the time of implant and appropriate programming may improve the effectiveness of cardiac resynchronization therapy (CRT) in this patient population.
Conclusion: Our case series emphasizes the need for a registry in the absence of randomized controlled trials, in order to identify patients who benefit most from CRT, and, importantly, recognize subgroups that respond poorly.     

心脏再同步化治疗充血性心力衰竭并发症的观察及护理

目的观察心脏再同步化治疗（CRT）充血性心力衰竭（CHF）患者并发症的疗效及护理。方法对12例CHF患者进行CRT，观察手术期并发症，并给予一定护理措施。结果12例患者中, 10例无并发症发生，2例并发冠状窦静脉夹层瘤。结论正确指导配合科学护理可有效减少CHF患者手术期并发症，是CRT植入手术成功的重要保障。     

Elevated estimated pulmonary artery systolic pressure is associated with an adverse clinical outcome in patients receiving cardiac resynchronization therapy

BACKGROUND: A substantial percentage of patients with heart failure remain nonresponsive to cardiac resynchronization therapy (CRT). There is a paucity of information on the impact of baseline elevated pulmonary artery pressure on clinical outcome and on left ventricular reverse remodeling (LV-RR) after CRT. We sought to investigate the impact of elevated estimated pulmonary artery systolic pressure (ePASP) on clinical outcome and LV-RR after CRT. METHODS: This study retrospectively analyzed data from 68 subjects with standard indications for CRT over a 12-month period. Subjects were stratified into two groups based on the echocardiographic estimation of pulmonary artery pressure i.e., ePASP > or = 50 mmHg (n = 27) and ePASP < 50 mmHg (n = 41). Long-term response was measured as a combined endpoint of heart failure hospitalizations and all cause mortality at 12 months, and compared within the two groups using the Kaplan-Meier method. Follow up echocardiograms to assess for LV-RR were available in 51 subjects (mean duration 7.1 months). LV-RR was defined as any improvement in global systolic function with reduction in left ventricular internal diameter. RESULTS: The study population was composed of 24 women and 44 men (age, mean +/- SD; 70 +/- 11 years), with a decreased left ventricular ejection fraction ([25 +/- 9]%) and a wide QRS (171 +/- 54 ms). There were no significant differences in the clinical features between the high and low ePASP group. Subjects with ePASP > or = 50 mmHg had a significantly worse clinical outcome (Hazard ratio (95% CI), 2.0 (1.2-5.5), P = 0.02). Baseline ePASP was not predictive of LV-RR (P = 0.32). CONCLUSION: In patients receiving CRT, although elevated estimated pulmonary artery systolic pressure (ePASP > or = 50 mmHg) does not significantly impact LV reverse remodeling, it is associated with an adverse long-term outcome.     

Greater three-dimensional ventricular lead tip separation is associated with improved outcome after cardiac resynchronization therapy

Background: Effective cardiac resynchronization therapy (CRT) is more likely with widely separated left ventricular (LV) and right ventricular (RV) pacing leads tips. We hypothesized that lead separation is an important factor in determining the clinical response to CRT. Methods: A retrospective study of 86 consecutive patients age 71 ± 10 years, male (74%), coronary disease (71%), atrial fibrillation (23%), LV ejection fraction (22 ± 9%), QRS duration (160 ± 27 ms), New York Heart Association (NYHA) class III (81%), NYHA class IV (19%) undergoing CRT from January 2006 to September 2008. The median follow‐up was 12 months and clinical response to CRT was defined as reduction of NYHA class by one or more. The three‐dimensional separation between RV and LV pacing lead tips was calculated using measurements obtained from orthogonal posteroanterior and lateral chest radiographs performed the day after implantation. Results: Fifty‐nine patients (69%) responded to CRT. There was a statistically significant association between increased three‐dimensional lead separation and clinical response to CRT (P= 0.005). Stronger association was obtained when lead separation was corrected for cardiac size (P= 0.001). A significantly higher response rate of 88% was achieved in patients with QRS duration of 160 ms or more, and lead separation of 100 mm or more compared with 60% when lead separation was less than 100 mm and QRS duration remained the same (P = 0.027). Conclusions: Greater three‐dimensional separation of LV‐to‐RV leads is associated with improved response to CRT. A prospective multicenter trial is needed to assess lead separation as a predictor for response. (PACE 2010; 33:1490–1496)     

心脏再同步化治疗适应证的变迁

心脏再同步化治疗(CRT)慢性心力衰竭已走过20个春秋,其疗效已得到充分的肯定.随着系列临床研究结果的揭晓,其适应证也不断发生改变.从1998年最早的Ⅱb(C)类适应证,逐步发展到Ⅰ(A)类适应证;从纽约心脏病协会(NYHA)心功能Ⅲ或Ⅳ级拓展到Ⅰ～Ⅱ级;从窦性心律患者发展到心房颤动患者.对起搏依赖的心力衰竭患者其适应证变化也很大,从Ⅱb类适应证进展到Ⅰ(B)适应证,并且对左心室射血分数(LVEF)降低没有严格限制,其目的是为了防止大量右心室起搏给心力衰竭患者带来的危害,使患者达到最大获益.然而在QRS时限及形态的掌握上更加严格.目前认为,对QRS时限≥150 ms及完全性左束支传导阻滞(LBBB)患者,CRT治疗的获益最大,已经否定了对窄QRS时限(＜120 ms)的疗效.我们相信随着循证医学证据的积累,CRT治疗的目标人群会更加明确和具体,CRT应答率会进一步提高.     

Living with cardiac resynchronization therapy: Challenges for people with heart failure

The number of people with heart failure requiring implantation of a cardiac resynchronization device is increasing in Iran. Although this intervention is an effective life‐saving treatment, several challenges are associated with patients’ lifestyle after insertion. This study identified the challenges and coping mechanisms of Iranians with heart failure living with cardiac resynchronization therapy. A qualitative approach using conventional content analysis was adopted. Seventeen people with heart failure and three nurses were recruited between December 2014 and November 2015 from a teaching hospital and a private clinic in Rasht, Iran. Participants were interviewed using semi‐structured interviews lasting 30–60 min. Five themes emerged: (i) fear of implantation, (ii) the panic of receiving a shock from the device, (iii) lack of control over life, (iv) inadequacies of the healthcare system, and (v) psychosocial coping. A heightened understanding of these challenges and coping strategies could prepare healthcare professionals to provide better routine care, education, and support to the recipients of cardiac resynchronization therapy prior to implantation, during the recovery period, and for long‐term management.     

Cardiac resynchronization therapy in patients with minimally symptomatic heart failure

Cardiac resynchronization therapy improves mortality and heart failure symptoms in patients with sinus rhythm, depressed left ventricular ejection fraction, a wide QRS complex and moderate-to-severe heart failure symptoms. The results of recent trials suggest that in similar patients with minimal heart failure symptoms cardiac resynchronization therapy is associated with left ventricular reverse remodeling, and may prevent the progression of heart failure.     

Antiarrhythmic effect of reverse electrical remodeling associated with cardiac resynchronization therapy

Background: Antiarrhythmic and proarrhythmic effects of cardiac resynchronization therapy (CRT) remain controversial. We hypothesized that reverse electrical remodeling (RER) with CRT is associated with reduced frequency of ventricular tachyarrhythmias (VTs). Methods: The width of native and paced QRS was measured in lead II electrocardiogram before and 13 ± 7 months after implantation of a CRT defibrillator device in 69 patients (mean age 66.3 ± 13.9; 39 males [83%]) with bundle branch block (BBB) (41 patients with left BBB and three patients with bifascicular block) or nonspecific intraventricular conduction delay (25 patients, 36%), and New York Heart Association class III–IV heart failure. Biventricular pacing was inhibited for 10 seconds to record native QRS. RER was defined as a decrease in the native QRS duration ≥10 ms compared to preimplant. Patients were followed prospectively 24 ± 13 months after assessment for electrical remodeling. Results: RER was observed in 22 patients (32%), among whom QRS duration decreased by 30.9 ± 14.1 ms (P < 0.00001) with similar heart rate and QRS morphology. Native QRS duration increased by 10.3 ± 16.6 ms in the other 47 patients (68%) (P = 0.0001). Baseline mean ejection fraction did not differ between patients with and those without RER (24.9 ± 10.0 vs 24.2 ± 8.6%, NS). During 2 ± 1 years of further follow‐up, 19 patients had VTs and 12 patients died. RER was associated with a fourfold decrease in the risk of death or sustained VTs requiring appropriate implantable cardioverter‐defibrillator therapies, whichever came first (hazard ratio 0.25; 95% confidence interval 0.08–0.85; P = 0.026). Conclusion: RER of the native conduction with CRT is associated with decreased mortality and antiarrhythmic effect of CRT. (PACE 2011; 34:357–364)     

Cardiac resynchronization therapy and automatic implantable cardiac defibrillators in the treatment of heart failure: a review article

PURPOSE: To review the use of cardiac resynchronization therapy (CRT) and automatic implantable cardiac defibrillators (AICDs) in heart failure (HF) patients. DATA SOURCES: Selected scientific literature. CONCLUSIONS: New developments in device therapy for HF patients are helping to decrease morbidity and mortality in this challenging patient population. CRT improves left ventricular (LV) ejection fraction, quality of life, 6-min walk distances, and New York Heart Association scores in select patients. AICDs can prevent sudden cardiac death in those who have LV dysfunction and are at risk for ventricular arrhythmias. Cardiac devices are now becoming a standard of care for those with HF who meet certain criteria. IMPLICATIONS FOR PRACTICE: Despite advances in medical therapy for treating LV dysfunction, newly diagnosed patients face a 50% mortality rate in 5 years. The natural history of HF leads to continual deterioration of function unless adverse cardiac remodeling is reversed. Until recently, the only means for improving symptoms and cardiac function has been through the optimization of standard medicines that are indicated for LV dysfunction, such as angiotensin-converting enzyme inhibitors and beta-blockers. However, not all patients benefit from medical management alone. Cardiac devices may now be considered when significant symptoms persist after standard medicines are optimized. When practitioners use a multiple-modality approach, careful patient selection based on the inclusion criteria used in the trials outlined in this article will likely lead to improved management of those with LV dysfunction.     

Mood disorders and outcome in patients receiving cardiac resynchronization therapy

Background: Mood disorders (MD) have been demonstrated to influence outcome in cardiac disease in general and specifically in chronic heart failure (HF). Little is known about their possible effect on response to cardiac resynchronization therapy (CRT). Objective: To evaluate the influence of MD on CRT response. Methods: We conducted a retrospective chart review of all cardiac CRT‐D (CRT defibrillator) recipients (N = 153) at the Veterans Affairs Pittsburgh Healthcare System from beginning of 2004 through end of 2006. All‐cause death and HF‐related hospitalizations (HFH), individually and combined, were sought through 2009. Results: During a mean follow‐up time of 31.4 ± 14.7 months, there were 48 (31.4%) deaths and 55 (35.9%) HFHs in HF patients having New York Heart Association class of 2.9 ± 0.3, left ventricular ejection fraction (LVEF) of 25.8 ± 9.1%, left ventricular end‐diastolic diameter (LVEDD) of 61.6 ± 11.6 mm, and QRS of 152 ± 30.5 ms . A total of 65 (42.5%) patients had MD (depression, anxiety, or posttraumatic stress disorder). Compared to others, patients in the MD group were at a significantly higher risk of HFH alone (47.7% vs 27.3%, P = 0.009) or when combined with death (58.5% vs 39.8%, P = 0.022) but not death alone (35.4% vs 28.4%, P = 0.36). The significant predictive effect of MD on HFH alone and when combined with death shown in univariate analysis was not attenuated after adjustment for age, ejection fraction, etiology of cardiomyopathy, cumulative number of any shocks, smoking, and evidence of postimplantation echocardiographic improvement. Conclusions: MD in patients with advanced but stable HF receiving CRT‐D therapy was a predictor of HFH alone or when combined with death but not mortality alone. (PACE 2011;1–9)     

Complications associated with cardiac resynchronization therapy upgrades versus de novo implantations

Introduction: A significant number of patients undergo upgrade to cardiac resynchronization therapy (CRT). These patients tend to differ from individuals undergoing de novo CRT implantations both in terms of their baseline demographics and the etiology underlying their heart failure.

Areas covered: There are several factors that need to be considered when upgrading patients to CRT, such as, venous patency. Potentially, these conditions can cause issues which may result in procedures being more difficult than de novo implantations. This article discusses these issues and compares the rates of procedural-related complications for CRT upgrades and de novo implantations. It discusses the proportion of patients that are likely to respond to CRT with each intervention.

Expert commentary: Understanding the relative risks of CRT upgrades versus de novo implantations is important to help operators select the correct initial device and counsel patients accordingly. Growing experience with image-guided implantations and endocardial pacing may prove to be particularly relevant to patients undergoing CRT upgrades.     

Antiinflammatory effects of cardiac resynchronization therapy in patients with chronic heart failure

BACKGROUND: Cardiac resynchronization therapy (CRT) pacing has been proposed as an additional treatment to medical therapy to improve heart failure patients with left ventricular asynchrony. The aim of this study was to evaluate the influence of CRT treatment on proinflammatory cytokines in patients with heart failure. METHODS: Twenty patients, with a mean age 64 +/- 2 years, with severe chronic heart failure NYHA class II-IV (mean ejection fraction 25 +/- 2%), were included in the study. Patients were treated with CRT pacing, after failure of optimal therapy. Blood samples were taken at baseline, 3 months after pacing therapy, and after a subsequent 3-month period of no pacing for the assessment of proinflammatory cytokines TNF-alpha and its receptors (sTNFR-I, sTNFR-II), IL-6, adhesion molecules sICAM-1 and sVCAM-1, and the apoptotic indices sFas and sFas-Ligand. RESULTS: Levels of TNF-alpha, sTNFR-I, and sTNFR-II were reduced at the end of 3 months of CRT therapy and further reduced at the end of the no pacing period (P < 0.05, compared to baseline). Levels of IL-6 also declined after 3 months of CRT pacing (from 8.9 +/- 2.5 pg/mL to 4.7 +/- 1.3 pg/mL, P < 0.05) and this was maintained during the no pacing period (3.9 +/- 1.1 pg/mL P < 0.05 compared to baseline). The adhesion molecule sICAM-1 levels also reduced (from 265 +/- 17 ng/mL to 235 +/- 12, P < 0.05) after 3 months of CRT pacing and remained unchanged at the end of the no pacing period (219 +/- 12 ng/mL, P < 0.05 compared to baseline values). CONCLUSION: Major proinflammatory cytokines and the adhesion molecule sICAM-1 are reduced with CRT therapy and this effect is maintained for at least 3 months after discontinuation of pacing.     

Gender disparity in the use of cardiac resynchronization therapy in the United States

Background: Although several studies have shown the effectiveness of cardiac resynchronization therapy (CRT) for advanced congestive heart failure (CHF), gender differences in utilization of CRT are not known.
Methods: We used the Healthcare Cost and Utilization Project (HCUP) to study national rates for admissions due to CHF along with procedures for initial CRT implantation, including both CRT-defibrillator (CRT-D) and CRT-pacemakers (CRT-P) during the years of 2002–2004. Chi-square tests were used for comparison between number of women and men. A P < 0.05 was considered significant.
Result: Women had consistently higher rates of admission for CHF during each year (574,037 (54%) vs 482,005 (46%), 2002; 601,181 (54%) vs 517,202 (46%), 2003; and 580,913 (53%) vs 521,280 (47%), 2004). The number of initial CRT device implantations (both CRT-D and CRT-P) was significantly lower during each year for women compared to men (659 (25%) vs 1,931 (75%), 2002; 6,928 (26%) vs 19,646 (74%), 2003; and 11,286 (27%) vs 42,196 (73%), 2004; P < 0.01 for all). Both CRT-P and CRT-D were used less frequently in women compared to men; however, this difference was consistently less prominent during each year with CRT-P compared to CRT-D (301 (41%) CRT-P vs 358 (19%) CRT-D, 2002; 659 (39%) CRT-P vs 2,530 (28%) CRT-D, 2003; and 2,891 (39%) CRT-P vs 8,395 (24%) CRT-D, 2004; P < 0.05).
Conclusion: Our data clearly demonstrate a significant gender disparity in utilization of CRT devices. Further studies are needed to find possible reasons behind this disparity.     

Application of the Seattle Heart Failure Model in patients on cardiac resynchronization therapy

Background: The Seattle Heart Failure Model (SHFM) is a multimarker risk assessment tool able to predict outcome in heart failure (HF) patients. Aim: To assess whether the SHFM can be used to risk‐stratify HF patients who underwent cardiac resynchronization therapy with (CRT‐D) or without (CRT) an implantable defibrillator. Methods and Results: The SHFM was applied to 342 New York Heart Association class III‐IV patients who received a CRT (23%) or CRT‐D (77%) device. Discrimination and calibration of SHFM were evaluated through c‐statistics and Hosmer‐Lemeshow (H‐L) goodness‐of‐fit test. Primary endpoint was a composite of death from any cause/cardiac transplantation. During a median follow‐up of 24 months (25th–75th percentile [pct]: 12–37 months), 78 of 342 (22.8%) patients died; seven patients underwent urgent transplantation. Median SHFM score for patients with endpoint was 5.8 years (25th–75th pct: 4.25–8.7 years) versus 8.9 years (25th–75th pct: 6.6–11.8 years) for those without (P < 0.001). Discrimination of SHFM was adequate for the endpoint (c‐statistic always ranged around 0.7). The SHFM was a good fit of death from any cause/cardiac transplantation, without significant differences between observed and SHFM‐predicted survival. Conclusion: The SHFM successfully stratifies HF patients on CRT/CRT‐D and can be reliably applied to help clinicians in predicting survival in this clinical setting. (PACE 2012; 35:88–94)