Comorbidity Significantly Affects Clinical Outcome After Cardiac Resynchronization Therapy Regardless of Ventricular Remodeling

doi:10.1016/j.cardfail.2012.09.003

Journal of Cardiac Failure

Volume 18, Issue 11, November 2012, Pages 845-853

https://doi.org/10.1016/j.cardfail.2012.09.003 Get rights and content

Abstract

Background

The influence of comorbid conditions on ventricular remodeling, functional status, and clinical outcome after cardiac resynchronization therapy (CRT) is insufficiently elucidated.

Methods and Results

The influence of different comorbid conditions on left ventricular remodeling, improvement in New York Heart Association (NYHA) functional class, hospitalizations for heart failure, and all-cause mortality after CRT implantation was analyzed in 172 consecutive patients (mean age 71 ± 9 y), implanted from October 2008 to April 2011 in a single tertiary care hospital. During mean follow-up of 18 ± 9 months, 21 patients died and 57 were admitted for heart failure. Left ventricular remodeling and improvement in NYHA functional class were independent from comorbidity burden. However, diabetes mellitus (hazard ratio [HR] 3.45, 95% confidence interval [CI] 1.24–9.65) and chronic kidney disease (HR 3.11, 95% CI 1.10–8.81) were predictors of all-cause mortality, and the presence of chronic obstructive pulmonary disease (HR 1.89, 95% CI 1.02–3.53) was independently associated with heart failure admissions. Importantly, those 3 comorbid conditions had an additive negative impact on survival and heart failure admissions, even in patients with reverse left ventricular remodeling.

Conclusions

Reverse ventricular remodeling and improvement in functional status after CRT implantation are independent from comorbidity burden. However, comorbid conditions remain important predictors of all-cause mortality and heart failure admissions.

Section snippets

Study Population

We evaluated 172 consecutive CHF patients who received a CRT device in a single tertiary care center (Ziekenhuis Oost-Limburg, Genk, Belgium) from October 1, 2008, to April 30, 2011. Patients had a LVEF ≤35% and a QRS duration ≥120 ms, and they were mostly in NYHA functional class III or IV despite optimal medical treatment, as consistent with current guideline recommendations for CRT.12, 13 The decision to use a CRT device with defibrillator function (CRT-D) was based on local reimbursement

Baseline Patient Characteristics

Baseline characteristics of the study population are summarized in Table 1. The prevalence of comorbid conditions was high in this cohort of patients with advanced CHF, as presented in Table 2. Survivors and nonsurvivors had similar baseline characteristics with respect to age, sex, and etiology of heart failure. However, nonsurvivors had a higher NYHA functional class and worse right ventricular function with a higher degree of tricuspid valve regurgitation, and they used loop diuretics more

Discussion

The key finding of the present retrospective study is that reverse ventricular remodeling after implantation of a CRT device in patients with advanced CHF is not affected by comorbidity burden. Additionally, patients with comorbid conditions experienced a similar improvement in functional status (assessed by NYHA functional class) after implantation. However, 3 comorbid conditions (diabetes mellitus, chronic kidney disease, and COPD) had a significant and additive negative impact on death and

Clinical Implications

The present observations highlight the limitations of generally used definitions of response to CRT in most clinical trials that are based on the presence of reverse remodeling, symptomatic relief, or reduced adverse events. Current selection criteria for CRT, based on wide QRS and the presence of poor LVEF on echocardiography, seem to predict reverse ventricular remodeling as well as clinical response to CRT (ie, better functional capacity). However, comorbidity burden is likely to be at least

Study Limitations

Some study limitations should be taken into account. First, the retrospective study design might have led to differences in the study population subgroups that could also account for the observed differences. For example, more advanced NYHA functional class, worse right ventricular function, more severe tricuspid valve regurgitation, and higher prevalence of loop diuretic use were present in patients who died, and ischemic etiology for heart failure and use of loop diuretics were more prevalent

Conclusion

Comorbidity burden significantly affects clinical outcome after CRT (ie, all-cause mortality and heart failure admissions) in patients with advanced CHF and conventional guideline indications for CRT, regardless of left ventricular remodeling and functional improvement.

Disclosures

Dr. Tang and Dr. Mullens are consultants to Medtronic and St Jude Medical. All of the other authors report no potential conflict of interest.

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Cited by (30)

What Have We Learned in the Last 20 Years About CRT Non-Responders?
2022, Cardiac Electrophysiology Clinics
Citation Excerpt :
In particular, although patients with DM do still receive benefit from CRT,33,34 a meta-analysis has shown a higher mortality in diabetic patients.35 This has also been observed in large real-world registry studies31,36 which have shown that HbA1c, as an expression of poor glycaemic control, is predictive of a worse CRT outcome.37 Similar studies also suggest a reduction in reverse remodeling following CRT in patients with DM despite similar levels of resynchronization.38,39
Case Studies of Cardiac Resynchronization Therapy “Nonresponders”
2022, Cardiac Electrophysiology Clinics
Impact of baseline renal function on all-cause mortality in patients who underwent cardiac resynchronization therapy: A systematic review and meta-analysis
2017, Journal of Arrhythmia
Citation Excerpt :
Subsequently, 178 studies were excluded at the title/abstract level, and 31 studies were excluded at the full text level, according to the criteria mentioned above. As a result, 16 studies [13–28] satisfied our inclusion criteria and were included in our analysis. Of the 16 studies included in this analysis, 13 demonstrated that baseline renal dysfunction had a significant adverse effect on all-cause mortality in patients who underwent CRT, and the remaining three studies did not.
Cardiac resynchronization therapy (CRT) improves both morbidity and mortality in selected patients with heart failure and increased QRS duration. However, chronic kidney disease (CKD) may have an adverse effect on patient outcome. The aim of this systematic review was to analyze the existing data regarding the impact of baseline renal function on all-cause mortality in patients who underwent CRT.
Medline database was searched systematically, and studies evaluating the effect of baseline renal function on all-cause mortality in patients who underwent CRT were retrieved. We performed three separate analyses according to the comparison groups included in each study. Data were analyzed using Review Manager software (RevMan version 5.3; Oxford, UK).
We included 16 relevant studies in our analysis. Specifically, 13 studies showed a statistically significant higher risk of all-cause mortality in patients with impaired baseline renal function who underwent CRT. The remaining three studies did not show a statistically significant result. The quantitative synthesis of five studies showed a 19% decrease in all-cause mortality per 10-unit increment in estimated glomerular filtration rate (eGFR) [HR: 0.81, 95% CI (0.73–0.90), p<0.01, 86% I²]. Additionally, we demonstrated that patients with an eGFR<60 mL/min/1.73 m² had an all-cause mortality rate of 66% [HR: 1.66, 95% CI (1.37–2.02), p<0.01, 0% I²], which was higher than in those with an eGFR≥60 mL/min/1.73 m².
Baseline renal dysfunction has an adverse effect on-all cause mortality in patients who underwent CRT.
Multiple Comorbidities and Response to Cardiac Resynchronization Therapy: MADIT-CRT Long-Term Follow-Up
2017, Journal of the American College of Cardiology
Data regarding cardiac resynchronization therapy (CRT) in patients with multiple comorbidities are limited.
This study evaluated the association of multiple comorbidities with the benefits of CRT over implantable cardioverter-defibrillator (ICD) alone.
We examined 1,214 MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) study patients with left bundle branch block (LBBB) and 0, 1, 2, or ≥3 comorbidities, including renal dysfunction, hypertension (HTN), diabetes, coronary artery disease, history of atrial arrhythmias, history of ventricular arrhythmias, current smoking, and cerebrovascular accident. In an adjusted analysis, we analyzed risk of heart failure (HF) events or death by comorbidity group in all patients and in patients with CRT with defibrillator (CRT-D) versus ICD. Then we examined percent change in left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV ejection fraction, left atrial volume, and LV dyssynchrony at 1-year in CRT-D patients by comorbidity group.
There was an inverse relationship between comorbidity burden and improvements in LV end-systolic volume, LV end-diastolic volume, left ventricular ejection fraction, left atrial volume, and LV dyssynchrony. In an adjusted model, there was an increasing risk of death or nonfatal HF events with increasing comorbidity burden regardless of treatment group (p < 0.001). During a mean follow-up of 4.65 years, there was no interaction with respect to comorbidity burden and the benefit of CRT-D versus ICD only for death or nonfatal HF events (interaction p = 0.943). In the groups with greatest comorbidity burden (2 and ≥3), the absolute risk reduction associated with CRT-D over ICD alone appeared greater than that seen for groups with less comorbidity burden (0 and 1).
During long-term follow-up of MADIT-CRT study patients with LBBB randomized to CRT-D, there were differences in HF or death risk and in the degree of reverse remodeling among comorbidity groups. However, the burden of comorbidity does not appear to compromise the clinical benefits of CRT-D compared with ICD alone.
Impact of Iron Deficiency on Response to and Remodeling After Cardiac Resynchronization Therapy
2017, American Journal of Cardiology
Citation Excerpt :
We also confirm previous findings that iron deficiency is often present even in the absence of anemia.6 In the setting of patients with heart failure with a high prevalence of co-morbidities, it is important to appreciate that symptomatic response not always neatly tracks echocardiographic response (reverse remodeling) or vice versa.17 Results of the present study indicate that iron deficiency in CRT recipients influences the clinical response to CRT.
Iron deficiency is prevalent in heart failure with reduced ejection fraction and relates to symptomatic status, readmission, and all-cause mortality. The relation between iron status and response to cardiac resynchronization therapy (CRT) remains insufficiently elucidated. This study assesses the impact of iron deficiency on clinical response and reverse cardiac remodeling and outcome after CRT. Baseline characteristics, change in New York Heart Association functional class, reverse cardiac remodeling on echocardiography, and clinical outcome (i.e., all-cause mortality and heart failure readmissions) were retrospectively evaluated in consecutive CRT patients who had full iron status and complete blood count available at implantation, implanted at a single tertiary care center with identical dedicated multidisciplinary CRT follow-up from October 2008 to August 2015. A total of 541 patients were included with mean follow-up of 38 ± 22 months. Prevalence of iron deficiency was 56% at implantation. Patients with iron deficiency exhibited less symptomatic improvement 6 months after implantation (p value <0.001). In addition, both the decrease in left ventricular end-diastolic diameter (−3.1 vs −6.2 mm; p value = 0.011) and improvement in ejection fraction (+11% vs +15%, p value = 0.001) were significantly lower in patients with iron deficiency. Iron deficiency was significantly associated with an increased risk for heart failure admission or all-cause mortality (adjusted hazard ratio 1.718, 95% confidence interval 1.178 to 2.506), irrespectively of the presence of anemia (Hemoglobin <12 g/dl in women and <13 g/dl in men). In conclusion, iron deficiency is prevalent and affects both clinical response and reverse cardiac remodeling after CRT implantation. Moreover, it is a powerful predictor of adverse clinical outcomes in CRT.
Special Issue: Latest Advances in Delivery and Outcomes of Cardiac Resynchronization Therapy and Conduction System Pacing
2023, Journal of Clinical Medicine

View all citing articles on Scopus

: This study is part of the Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital.

: See page 852 for disclosure information.

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Clinical InvestigationComorbidity Significantly Affects Clinical Outcome After Cardiac Resynchronization Therapy Regardless of Ventricular Remodeling

Abstract

Background

Methods and Results

Conclusions

Section snippets

Study Population

Baseline Patient Characteristics

Discussion

Clinical Implications

Study Limitations

Conclusion

Disclosures

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Heart Rhythm

Can J Cardiol

J Card Fail

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure

N Engl J Med

The effect of cardiac resynchronization on morbidity and mortality in heart failure

N Engl J Med

Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the Cardiac Resynchronization–Heart Failure (CARE-HF) trial extension phase]

Eur Heart J

Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials

Eur Heart J

Cardiac-resynchronization therapy for the prevention of heart-failure events

N Engl J Med

Clinical Investigation
Comorbidity Significantly Affects Clinical Outcome After Cardiac Resynchronization Therapy Regardless of Ventricular Remodeling