Male gender and chronic obstructive pulmonary disease predict a poor clinical response in patients undergoing cardiac resynchronisation therapy

Aims: Current guidelines advocate cardiac resynchronisation therapy (CRT) in patients with class III/IV New York Heart Association (NYHA) heart failure, depressed left ventricular function and a broad QRS. However, a significant proportion of patients do not derive any benefit from CRT. The aim of this study was to identify clinical, electrocardiographic and echocardiographic predictors of response to CRT. Methods: A retrospective analysis of patients undergoing CRT in our institution was performed. A favourable clinical response to CRT was defined as an improvement in NYHA Heart failure class of ≥ 1 and lack of hospitalisation with heart failure. Comparisons were made between responders and non‐responders in terms of baseline characteristics and potential predictors of CRT response (QRS width, presence of left bundle branch block, atrial fibrillation, evidence of mechanical dyssynchrony on echocardiography and LV lead position). Results: A total of 164 patients had full follow‐up data. The mean follow‐up was 293 days. Of patients undergoing CRT, 90 (58.9%) had a favourable clinical response to CRT. Predictors of a lack of clinical response to CRT were male gender (p = 0.012) and chronic obstructive pulmonary disease (COPD) (0.008). Pre‐implant echocardiographic dyssynchrony assessment appeared not to predict response to CRT (p = 0.87); however, there was a trend towards a positive response in those patients with significant dyssynchrony (p = 0.09) defined as interventricular delay > 40 ms or maximal LV delay of > 80 ms. Conclusion: Male gender and coexisting COPD were shown to be independent predictors of non‐response to CRT in this cohort of patients fulfilling current criteria for CRT.     

Improvement of congestive heart failure by upgrading of conventional to resynchronization pacemakers

AIMS: To compare the clinical response of patients with right ventricular apical pacing (RVAP) upgraded to cardiac resynchronization therapy (CRT) to that of previously nonpaced heart failure (HF) patients who had de novo CRT implantation. BACKGROUND: The role of CRT in patients with wide QRS and HF due to RVAP is less well established than in other CRT candidates. METHODS: Ninety-eight consecutive patients with CRT were studied (mean age 70, mean ejection fraction 0.23). Group A: patients having RVAP prior to CRT implantation (n = 25), group B: patients without prior RVAP (n = 73). Clinical and echocardiographic parameters were recorded prior to, and 3 months after, CRT implantation. RESULTS: Group A patients had a wider QRS at baseline compared to group B (203 +/- 32 ms vs 163 +/- 30 ms respectively, P < 0.001), and a shorter 6-minute walking distance (222 +/- 118 m vs 362 +/- 119 m, respectively, P < 0.005). Otherwise, clinical and echocardiographic parameters were not different. At follow up, group A patients had an average 0.7 +/- 0.5 decrease in their NYHA functional class, compared to 0.3 +/- 0.7 in group B patients (P < 0.05). Six-minute walking distance increased by 93 +/- 113 m in group A, versus 36 +/- 120 m in group B (P = 0.22). There was no difference in echocardiographic response to CRT between the groups. CONCLUSIONS: HF patients with prior RVAP demonstrate clinical improvement after upgrading to CRT that is comparable, and in some aspects, even better than that observed in HF patients with native conduction delay who undergo de novo CRT implantation.     

Cardiac resynchronization therapy response is associated with shorter duration of atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is commonly associated with heart failure. The benefit of cardiac resynchronization therapy (CRT) on atrial remodeling has been demonstrated. However, biventricular pacing did not reduce the global incidence of AF. We evaluated the relationship between CRT response and AF duration. METHODS: We retrospectively analyzed data from 96 patients (59 +/- 15 years; 78% male) who underwent CRT. All patients had class III-IV New York Heart Association (NYHA) symptoms despite maximal medical therapy, left ventricular ejection fraction (LVEF) < or = 35%, QRS >130 ms, and sinus rhythm before implantation. CRT response in patients who survived at six months of follow-up was defined as: (1) no hospitalization for heart failure and (2) improvement of one or more grades in the NYHA classification. RESULTS: CRT responders (n = 54) and non-responders (n = 42) had similar baseline characteristics, including the incidence of persistent AF within six months before implantation. Six months after implantation, when compared to baseline, CRT responders exhibited a significant decrease in left atrial size (47.5 +/- 7.1 mm vs 44.6 +/- 7.7 mm, P < 0.01) and in the incidence of persistent AF (17% vs 2%, P = 0.02). At six months, CRT responders demonstrated shorter mean AF duration (7.5 +/- 43.3 hours vs 48.8 +/- 129.0 hours, P = 0.03) and lower incidence of persistent AF (2% vs 19%, P = 0.004) compared to nonresponders. CONCLUSION: CRT response is associated with a reversal of atrial remodeling and a shorter AF duration.     

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.     

The QRS narrowing index predicts reverse left ventricular remodeling following cardiac resynchronization therapy

Background: The relationship between QRS narrowing and response to cardiac resynchronization therapy (CRT) has been controversial. Objective: We sought to analyze the relationship between QRS narrowing and reverse remodeling in patients undergoing CRT, taking into account potential confounders including pre‐CRT QRS duration and underlying QRS morphology. Methods: We reviewed pre‐ and postimplant electrocardiograms and echocardiograms in a cohort of 233 patients undergoing the new implantation of a CRT device between December 2001 and September 2006. For inclusion in the final cohort, patients had New York Heart Association classes II–IV heart failure, left ventricular ejection fraction (LVEF) ≤ 40%, and QRS duration ≥120 ms. Response to CRT was defined as a reduction in left ventricular end‐systolic volume (LVESV) of ≥10%. A multivariate model was constructed to determine the relationship between QRS change and response to CRT. Results: Patients with QRS narrowing had significantly greater reductions in left ventricular end‐diastolic volume (LVEDV) (mL) (?26.5 ± 52.5 vs ?4.8 ± 44.0, P = 0.002) and LVESV (mL) (?34.0 ± 55.5 vs ?9.9 ± 45.8, P = 0.002) and improvement in LVEF (%) (8.9 ± 12.8 vs 4.5 ± 9.0, P = 0.007) than patients without narrowing. In univariate analysis, female gender (P = 0.0002), percent QRS narrowing from baseline (P = 0.008), lack of nitrate (P≤0.0001) and antiarrhythmic medication use (P = 0.01), lack of a nonspecific intraventricular conduction delay (=0.02), nonischemic cardiomyopathy (P = 0.003), and lower pre‐CRT LVEDV (P = 0.006) and LVESV [P = 0.01]) were associated with responders. In a multivariate model, QRS narrowing, indexed to the baseline QRS duration, remained strongly associated with response (odds ratio 0.08 [0.01–0.56], P = 0.01). Conclusions: After adjusting for potential confounders, QRS narrowing, indexed to baseline QRS duration, is associated with enhanced reverse ventricular remodeling following CRT. (PACE 2011; 34:604–611)     

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)     

The benefits of biventricular pacing in heart failure patients with narrow QRS, NYHA class II and right ventricular pacing

OBJECTIVE: To identify subgroups of heart failure patients who might benefit from biventricular pacing. BACKGROUND: Cardiac resynchronization therapy (CRT) improves the quality of life, New York Heart Association (NYHA) functional class, and exercise capacity and decreases hospitalizations for heart failure for patients who have severe heart failure and a wide QRS. It is unclear if other populations of heart failure patients would benefit from CRT. METHODS: One hundred forty-four consecutive heart failure patients who underwent CRT and completed 3 months of follow-up were reviewed. Demographic, echocardiographic, electrocardiographic, and clinical outcome data were analyzed to assess the relationship of functional class and QRS duration before device implantation to postimplant outcomes. RESULTS: There were 20, 88, and 36 patients in NYHA functional class II, III, and IV, respectively. Thirty-four patients had right ventricular pacing and another 29 patients had a QRS duration < or = 150 ms. Patients who were in NYHA functional class II at baseline had significant improvement in left ventricular ejection fraction and indices of left ventricular remodeling after CRT. Similar significant findings were seen in the subgroup with right ventricular pacing at baseline after CRT. However, in the subgroup with a narrow QRS duration, there were no significant changes in the indices of left ventricular remodeling or in the NYHA functional class and there was a significant increase in the QRS duration. For the study cohort as a whole, an improvement in NYHA functional class after CRT correlated with a significant decrease in adverse clinical outcomes. CONCLUSIONS: Heart failure patients who were in NYHA functional class II and those with right ventricular pacing appeared to benefit from CRT.     

Prediction of Response to Cardiac Resynchronization Therapy: The Selection of Candidates for CRT (SCART) Study

Background: The aim of this study was to evaluate the ability of baseline clinical and echocardiographic parameters to predict a positive response to CRT.
Methods: We analyzed 6-month data from the first 133 consecutive patients enrolled in a multicenter prospective study. These patients had symptomatic heart failure (HF) refractory to pharmacological therapy (NYHA class II–IV), left ventricular ejection fraction (LVEF) ≤35%, and prespecified electrocardiographic, echocardiographic or tissue Doppler imaging markers of left ventricular (LV) dyssynchrony.
Results: After a follow-up period of 6 months, 1 patient died and 13 were hospitalized for worsening HF. There were significant (P < 0.01) clinical, functional, and echocardiographic improvements that included: New York heart Association Class, Quality-of-Life Score, QRS duration, LVEF, LV end-diastolic and end-systolic diameter (LVESD), and severity of mitral regurgitation A positive response was documented in 90/133 (68%) patients who presented an improved clinical composite score associated to an increase in LVEF ≥ 5 units. A multivariate analysis identified that a smaller LVESD (OR = 0.957, 95% CI 0.920–0.996; P = 0.030) and longer interventricular mechanical delay (IVMD) (OR = 1.017, 95% CI 1.005–1.029, P = 0.007) as independent predictors of a positive response. Receiver-operating curve analysis showed that a positive response to CRT may be predicted in patients with IVMD > 44 ms (with a sensitivity of 66% and a specificity of 55%) or with LVESD < 60 mm (with a sensitivity of 66% and a specificity of 61%).
Conclusions: Our results confirm the limited value of QRS duration in the selection of patients for CRT.
A less-advanced stage of disease and echocardiographic evidence of interventricular dyssynchrony demonstrated to predict response to CRT, while intraventricular dyssynchrony did not predict response.     

Three Years of Cardiac Resynchronization Therapy: Could Superior Benefits be Obtained in Patients with Heart Failure and Narrow QRS?

Aim of the study: To examine the long-term effects of cardiac resynchronization therapy (CRT) in patients presenting with heart failure (HF) and QRS ≤120 ms.
Methods: This was a prospective, longitudinal study of 376 patients [mean age = 65 years, mean left ventricular (LV) ejection fraction (EF) = 29%, mean QRS duration =165 ms, mean distance covered during a 6-minute hall walk (6-MHW) = 325 m], who underwent successful implantation of CRT systems. The QRS duration at baseline was ≤120 ms in 45 patients (12%) who were not pre-selected by echocardiographic criteria of dyssynchrony, and >120 ms in the remaining 331 patients. The baseline characteristics of the 2 groups were similar. We evaluated indices of cardiac function, percentage of responders, and survival rates over a mean 28-month follow-up.
Results: Both groups experienced similar long-term increases in 6-MHW, and decreases in New York Heart Association functional class and LV end-systolic volume (all comparisons P < 0.0001 in both groups). Time interaction of changes in LVEF and percentage of responders were significantly different (P = 0.03 and P = 0.004, respectively), in favor of the narrow QRS group, where the changes were sustained and persisted at 2 and 3 years. The long-term death rate from HF was lower in the group with narrow than in the group with wide QRS complex (P = 0.04; log-rank test).
Conclusions: CRT confers considerable long-term clinical, functional, and survival benefits in patients presenting with HF and narrow QRS, not preselected by echocardiographic criteria of dyssynchrony. Caution is advised before denying CRT to these patients on the basis of QRS width only.     

Biventricular upgrading in patients with conventional pacing system and congestive heart failure: results and response predictors

BACKGROUND: There are few studies on cardiac resynchronization therapy (CRT) in heart failure (HF) patients with preexisting right ventricular (RV) pacing. The purpose of this study was to determine the efficacy of CRT upgrading in RV-paced patients and the predictivity of electromechanical dyssynchrony parameters (EDP) evaluated by standard echocardiography (ECHO) and tissue Doppler imaging (TDI). METHODS: Thirty-eight consecutive patients with HF [New York Heart Association (NYHA) class III or IV, LVEF < 35%], prior continuous RV pacing, and absence of atrial fibrillation were enrolled in the presence of a paced QRS > or = 150 ms and evaluated by ECHO and TDI. A responder was defined as a patient with a favorable change in NYHA class and neither HF hospitalization nor death, plus an absolute increase of LVEF > or = 10 units. RESULTS: At six-months follow-up, the whole study population had significant improvement in symptoms, systolic function, and QRS duration (P < 0.001); 32 (84%) patients had a favorable clinical outcome, 25 (66%) were considered responders according to the previous definition. Postimplant QRS was similarly reduced in both responders and nonresponders, whereas EDP had a significant improvement only in responders (P < 0.05). Using EDP, 23 (79%) patients were responders compared with 2 (22%) patients without mechanical dyssynchrony (P = 0.002). CONCLUSIONS: In HF patients with previous RV pacing, CRT is effective to improve clinical, functional outcome, and LV performance and to reduce electromechanical dyssynchrony in a large proportion of patients. Dyssynchrony evaluated by standard and TDI ECHO can be useful for CRT selection of paced patients.     

Long-Term Survival in Patients Treated with Cardiac Resynchronization Therapy: A 3-Year Follow-Up Study from the InSync/InSync ICD Italian Registry

Background: Studies reporting the long-term survival of patients treated with cardiac resynchronization therapy (CRT) outside the realm of randomized controlled trials are still lacking. The aim of this study was to quantify the survival of patients treated with CRT in clinical practice and to investigate the long-term effects of CRT on clinical status and echocardiographic parameters.
Methods: The study population consisted of 317 consecutive patients with implanted CRT devices from eight Italian University/Teaching Hospitals. The patients were enrolled in a national observational registry and had a minimum follow-up of 2 years. A visit was performed in surviving patients and mortality data were obtained by hospital file review or direct telephone contact.
Results: During the study period, 83 (26%) patients died. The rate of all-cause mortality was significantly higher in ischemic than nonischemic patients (14% vs 8%, P = 0.002). Multivariate analysis showed that ischemic etiology (HR 1.72, CI 1.06–2.79; P = 0.028) and New York Heart Association (NYHA) class IV (HR 2.87, CI 1.24–6.64; P = 0.014) were the strongest predictors of all-cause mortality. The effects of CRT persisted at long-term follow-up (for at least 2 years) in terms of NYHA class improvement, increase of left ventricular ejection fraction, decrease of QRS duration (all P = 0.0001), and reduction of left ventricular end-diastolic and end-systolic diameters (P = 0.024 and P = 0.011, respectively).
Conclusions: During long-term (3 years) follow-up after CRT, total mortality rate was 10%/year. The outcome of ischemic patients was worse mainly due to a higher rate of death from progressive heart failure. Ischemic etiology along with NYHA class IV was identified as predictors of death. Benefits of CRT in terms of clinical function and echocardiographic parameters persisted at the time of long-term follow-up.     

常用超声指标不能预测心脏再同步化治疗的疗效

目的 比较和评价常用的M型超声、频谱多普勒和组织多普勒指标在预测心脏再同步化治疗(CRT)疗效中的价值.方法 29例完成随访的CRT患者,评价心脏同步性的常用超声心动图参数包括室间隔与左室后壁间的收缩延迟时间(SPWMD)、肺动脉射血前时间(PPEI)、主动脉射血前时间(APED、速度达峰时间的标准差(Ts-SD)、心室间机械延迟(IVMD).以CRT后6个月,左室收缩末容积较治疗前减小≥10%为治疗有效.结果 CRT的有效率为68.97%.术后CRT无效组的SPWMD、PPEI、APEI和Ts-SD均无显著改变(均P＞0.05),CRT有效组的SPWMD、APEI和Ts-SD显著缩短(P＜0.05或P＜0.001),SPWMD、PPEI、APEI、Ts-SD和IVMD预测CRT疗效的ROC曲线下面积在0.41～0.57之间,且差异均无统计学意义(均P＞0.05).结论 常用的M型超声、频谱多普勒和组织多普勒指标均不能预测CRT疗效,有必要进行实时三维超声和斑点追踪显像等新技术参数预测CRT疗效的研究.     

Acute Left Ventricular Dyssynchrony Improvement Predicts Long-Term Benefit from Cardiac Resynchronization Therapy

Study Objective: To evaluate the relationship between acute response to cardiac resynchronization therapy (CRT) and long-term clinical outcome in patients with drug refractory heart failure.
Methods and Results: In 28 patients undergoing CRT implant, left ventricular (LV) dyssynchrony was evaluated by tissue Doppler imaging (TDI)-derived longitudinal strain by mean of septum-lateral basal asynchrony index (S-Li) and basal delayed longitudinal contraction (DLC). TDI measurements were made before, and 30 minutes and 1 year after implant. Baseline and 1-year follow-up New York Heart Association (NYHA) functional class, 6-minute walking test (6-MWT) distance, and quality of life (QoL) score were measured. Responders (n = 22) were defined by a ≥ 1 decrease in NYHA functional class and 6-MWT ≥25% at 1 year. At baseline, no differences were observed between responders and nonresponders in clinical and echocardiographic measurements. LV dyssynchrony acutely recovered only in responders 30 minutes after implantation, with a significant reduction in S-Li and DLC. Moreover, the percent decreases in S-Li and DLC were highly correlated with those observed in NYHA class (r = 0.70, and r = 0.81, respectively, P < 0.001), 6-MWT (r = 0.59, and r = 0.57, respectively, P < 0.001 and P < 0.01), and QoL score (r = 0.71, and r = 0.83, respectively, p < 0.001) at 1-year follow-up.
Conclusions: Acute recovery of LV intraventricular dyssynchrony is a major discriminator between responders and nonresponders to CRT, which strongly correlates with a favorable long-term clinical outcome.     

Extraordinarily favorable left ventricular reverse remodeling through long-term cardiac resynchronization: super-response to cardiac resynchronization

Background: Some chronic heart failure (CHF) patients show remarkable improvement in left ventricular (LV) remodeling after cardiac resynchronization therapy (CRT), for unclear reasons. This study aimed at identifying predictors of an extraordinarily favorable response to CRT. Methods: We studied 136 CRT patients (104 men, median 66 years, QRS 162 ms, left ventricular ejection fraction 24 ± 7%, 70% coronary disease, all left bundle branch block [LBBB]). We measured LV end diastolic diameter (LVEDD) before and after long‐term (9.4 ± 6.3 months) CRT. At baseline, LV pre‐ejection interval (LVPEI), interventricular mechanical delay (IVMD), LV dyssynchrony (standard deviation of electromechanical delays [SDEMD] in eight LV segments), exercise capacity (pVO₂), and ventilatory efficiency (VE/VCO₂) were assessed. Patients with a LVEDD reduction beyond the 80th percentile (high responders [HR]) were compared to low responders (LR). Results: In the HR group (n = 22), LVEDD was reduced from 71 to 52 mm (LR 64–61 mm, P < 0.001). HR had predominantly nonischemic heart disease (HR: 72%, LR: 44%, P = 0.019), tended to have a wider QRS (HR: 178 ms, LR: 162 ms, P = 0.066), had a longer LVPEI (HR: 179 ms, LR: 155 ms, P = 0.004), wider IVMD (HR: 60 ms, LR 48 ms, P = 0.05), larger LVEDD (P = 0.002), higher SDEMD (HR: 69 ms, LR: 46 ms, P = 0.044), but higher pVO₂ (HR: 17.5 mL/min/kg, LR: 13.5 mL/kg/min, P = 0.025) and lower VE/VCO₂ (HR: 31, LR: 35, P = 0.043), all compared to LR patients. Conclusion: Extraordinarily favorable reverse LV remodeling through CRT in CHF and LBBB appears to require a particularly dilated LV due to nonischemic heart disease with pronounced electromechanical alteration, but with a fairly preserved functional capacity before CRT. (PACE 2012;XX:1–7)     

Does a Gender Difference in Response to Cardiac Resynchronization Therapy Exist?

BACKGROUND: Cardiac resynchronization therapy (CRT) has a beneficial effect on clinical symptoms, exercise capacity, and systolic left ventricular (LV) performance in patients with heart failure. The aim of the current study was to evaluate whether a gender difference exists in response to CRT. METHODS: Consecutive patients with end-stage heart failure (New York Heart Association, NYHA, class III-IV), LV ejection fraction (LVEF) < or =35%, QRS duration >120 ms, and left bundle branch block configuration underwent CRT. At baseline and 6 months post-CRT, clinical and echocardiographic parameters were evaluated; follow-up was obtained up to 5 years. The effects of CRT were compared between women and men. RESULTS: The study population comprised 137 men and 36 women (mean age 66 +/- 11 years). No differences in baseline characteristics were observed except that nonischemic cardiomyopathy was more frequent in women than men (67% vs 38%, P < 0.05). In all patients, clinical and echocardiographic parameters improved significantly at 6-month follow-up. The magnitude of improvement in different parameters was similar between women and men, e.g., the improvement in NYHA Class was 0.9 +/- 0.6 in women and 1.0 +/- 0.7 in men (NS) and the increase in LVEF was 8 +/- 8% in women as compared to 7 +/- 9% in men (NS). The percentage of individual responders was not different between women and men (76% vs 80%, NS) and 2-year survival was comparable for women and men (84% vs 80%, NS). CONCLUSION: No gender differences were observed in response to CRT and long-term survival after CRT.     

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)     

Time course of effects of cardiac resynchronization therapy in chronic heart failure: benefits in patients with preserved exercise capacity

Objectives: To assess in patients with chronic heart failure the effect of cardiac resynchronization therapy (CRT) over 12 months' follow-up the time course of the changes in functional and neurohormonal indices and to identify responders to CRT.
Methods: Eighty-nine patients (74.1 ± 1 years, left ventricular ejection fraction [LVEF] < 35%), QRS complex duration >150 ms, in stable New York Heart Association (NYHA) class III or IV on optimal medical treatment were prospectively randomized either in a control (n = 45) or CRT (n = 44) group and underwent clinical evaluation, cardiopulmonary exercise testing (CPET), 2D-Echo, heart rate variability (HRV), carotid baroreflex (BRS), and BNP assessments before and at 6- and 12-month follow-up.
Results: In the CRT group, improvement of cardiac indices and BNP concentration were evident at medium term (over 6 months) follow-up, and these changes persisted on a longer term (12 months) (all P < 0.05). Instead CPET indices and NYHA class improved after 12 months associated with restoration of HRV and BRS (all P < 0.05). We identified 26 responders to CRT according to changes in LVEF and diameters. Responders presented less depressed hemodynamic (LVEF 25 ± 1.0 vs 22 ± 0.1%), functional (peak VO₂ 10.2 ± 0.2 vs 6.9 ± 0.3 ml/kg/min), and neurohormonal indices (HRV 203.6 ± 15.7 vs 147.6 ± 10.ms, BRS 4.9 ± 0.2 vs 3.6 ± 0.3 ms/mmHg) (all P < 0.05). In the multivariate analysis, peak VO₂ was the strongest predictor of responders.
Conclusions: Improvement in functional status is associated with restoration of neurohormonal reflex control at medium term. Less depressed functional status (peak VO₂) was the strongest predictor of responders to CRT.     

Determinants of mortality in patients undergoing cardiac resynchronization therapy: baseline clinical, echocardiographic, and angioscintigraphic evaluation prior to resynchronization

BACKGROUND: In dilated cardiomyopathy (DCM) patients (pts) with cardiac resynchronization therapy (CRT) for ventricular dyssynchrony, long-term predictors of mortality and morbidity remain poorly investigated. METHOD AND RESULTS: We reviewed data of 102 pts, 68 +/- 10 years, NYHA Class II-IV (14 Class II, 67 Class III, 21 Class IV), who benefited from CRT (69 CRT, 33 CRT-ICD). Fifty-two patients had an ischemic DCM, 36 a previously implanted conventional PM/ICD, 29 a permanent atrial fibrillation, and 19 needed dobutamine in the month preceding implant. QRS duration was 187 +/- 35 ms, left ventricular end-diastolic diameter 72 +/- 10 mm, mitral regurgitation severity 1.9 +/- 0.8, echographic aorto-pulmonary electromechanical delay 61.5 +/- 25 ms and septo-lateral left intraventricular delay 86 +/- 56 ms, pulmonary artery pressure (PAP) 43 +/- 11 mmHg, angioscintigraphic left ventricular ejection fraction (EF) 20 +/- 9%, and right ventricular EF 30.5 +/- 14%. Over a mean follow-up of 23 +/- 20 months, 26 pts died (18 heart failures (HFs), 1 arrhythmic storm, 7 noncardiac deaths). Positive univariate predictors of death from any cause were NYHA Class IV (P < 0.001), and need for dobutamine the month preceding CRT (P < 0.008), while use of beta-blocking agents (P < 0.08) and left ventricular EF (P < 0.09) were negative ones. NYHA Class IV was the only independent predictor at multivariate analysis (P < 0.01). Survival at 24 months was 85% in Class II, 80% in Class III, and 37% in Class IV (II vs III, P = ns; III vs IV, P < 0.001). When using a composite endpoint of death from any cause and unplanned rehospitalization for a major cardiovascular event, there were 48 events (14 HF deaths, 3 noncardiac deaths, 26 HF rehospitalizations, 2 paroxysmal atrial fibrillation, 2 sustained ventricular tachycardia, 1 nonfatal pulmonary embolism). Predictors of death from any cause/unplanned rehospitalization for a major cardiovascular event in the follow-up were NYHA Class IV (P < 0.001), need for dobutamine during the month preceding CRT (P < 0.002), and PAP (<0.02). NYHA Class IV was the only independent predictor at multivariate analysis (P < 0.05). Event-free proportion at 24 months was 70% in Class II, 64% in Class III, and 37% in Class IV (II vs III, P = ns; III vs IV, P < 0.01). When considering determinants of mortality only in NYHA Class IV patients, no variable was significantly correlated to mortality. Need for dobutamine during the last month preceding CRT did not add an adjunctive mortality risk. CONCLUSION: Baseline NYHA Class IV at implantation appears as the most important determinant of a poor clinical outcome in terms of both mortality and morbidity. No predictive criteria seem available for NYHA Class IV patients, in order to discriminate who will die after CRT and who will not. NYHA Class IV strongly influences the clinical outcome, suggesting that, in future studies planned on mortality and rehospitalization as major endpoints, baseline NYHA Class IV should be separately taken into account.     

Non-invasive cardiac mapping for non-response in cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is an effective intervention in selected patients with moderate-to-severe heart failure with reduced ejection fraction and abnormal left ventricular activation time. The non-response rate of approximately 30% has remained nearly unchanged since this therapy was introduced 25 years ago. While intracardiac mapping is widely used for diagnosis and guidance of therapy in patients with tachyarrhythmia, its application in characterization of the electrical substrate to elucidate the mechanisms involved in CRT response remain anecdotal. In the present review, we describe the traditional determinants of CRT response before presenting novel non-invasive techniques used for CRT optimization. We discuss efforts to identify the target electrical substrate to guide the deployment of pacing electrodes during the operative procedure. Non-invasive body surface mapping technologies such as ECG imaging or ECG belt enables prediction of acute and chronic CRT response. While electrical dyssynchrony parameters provide high predictive accuracy for CRT response when obtained during intrinsic conduction, their predictive value is less when acquired during CRT or LV-pacing.

Key messages

• Classic predictors of CRT response are female gender, NYHA class ≤ III, left ventricular ejection fraction ≥25%, QRS duration ≥150 ms and estimated glomerular filtration rate ≥60 mL/min.
• ECG-imaging is a comprehensive non-invasive mapping system which allows to express the amount of electrical asynchrony of a CRT candidate.
• Non-invasive body surface mapping technologies enables excellent prediction of acute and chronic CRT response before implantation.
• When performed during CRT or LV-pacing, the added value of these mapping systems remains unclear.

     

Right Ventricular Myocardial Function in Patients with Either Idiopathic or Ischemic Dilated Cardiomyopathy Without Clinical Sign of Right Heart Failure: Effects of Cardiac Resynchronization Therapy

Objective: In dilated cardiomyopathy (DCM), right ventricular (RV) dysfunction has been reported and attributed both to altered loading conditions and to RV involvement in the myopathic process. The aim of the study was to detect RV myocardial function in DCM using two‐dimensional (2D) strain echocardiography and to assess the effects of cardiac resynchronization therapy (CRT) on RV myocardial strain during a 6‐month follow‐up. Methods and Results: A total of 110 patients (mean age: 55.4 ± 11.2 years) with either idiopathic (n = 60) or ischemic (n = 50) DCM, without overt clinical signs of RV failure, underwent standard echo and 2D strain analysis of RV longitudinal strain in RV septal and lateral walls. The two groups were comparable for clinical variables (New York Heart Association class III in 81.8%). Left ventricular volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler mitral and tricuspid inflow measurements. RV diameters were mildly increased in patients with idiopathic DCM, while RV tricuspid annulus systolic excursion and Tei‐index were comparable between the two groups. RV global longitudinal strain and regional peak myocardial strain were significantly impaired in patients with idiopathic DCM compared with those having ischemic DCM (all P < 0.001). Using left ventricular end‐systolic volume as marker for response to CRT, 70 patients (63.3%) were long‐term responders. Ischemic DCM patient responders to CRT showed a significant improvement in RV peak systolic strain. Conversely, in patients with idiopathic DCM and in ischemic patients nonresponders to CRT, no improvement in RV function was evidenced. By multivariable analysis, in the overall population, ischemic etiology of DCM (P < 0.0001), positive response to CRT (P < 0.001), and longitudinal intraventricular dyssynchrony (P <0.01) emerged as the only independent determinants of RV global longitudinal strain after CRT. Conclusions: Two‐dimensional strain represents a promising noninvasive technique to assess RV myocardial function in patients with DCM. RV myocardial deformation at baseline and after CRT are more impaired in idiopathic compared with ischemic DCM patients. Future longitudinal studies are warranted to understand the natural history of RV myocardial function, the extent of reversibility of RV dysfunction with CRT, and the possible prognostic impact of such indexes in patients with congestive heart failure.