Paul W.X. Foley

Cardiac resynchronization therapy guided by late gadolinium-enhancement cardiovascular magnetic resonance

BackgroundMyocardial scarring at the LV pacing site leads to incomplete resynchronization and a suboptimal symptomatic response to CRT. We sought to determine whether the use of late gadolinium cardiovascular magnetic resonance (LGE-CMR) to guide left ventricular (LV) lead deployment influences the long-term outcome of cardiac resynchronization therapy (CRT).Methods559 patients with heart failure (age 70.4 ± 10.7 yrs [mean ± SD]) due to ischemic or non-ischemic cardiomyopathy underwent CRT. Implantations were either guided (+CMR) or not guided (-CMR) by LGE-CMR prior to implantation. Fluoroscopy and LGE-CMR were used to localize the LV lead tip and and myocardial scarring retrospectively. Clinical events were assessed in three groups: +CMR and pacing scar (+CMR+S); CMR and not pacing scar (+CMR-S), and; LV pacing not guided by CMR (-CMR).ResultsOver a maximum follow-up of 9.1 yrs, +CMR+S had the highest risk of cardiovascular death (HR: 6.34), cardiovascular death or hospitalizations for heart failure (HR: 5.57) and death from any cause or hospitalizations for major adverse cardiovascular events (HR: 4.74) (all P < 0.0001), compared with +CMR-S. An intermediate risk of meeting these endpoints was observed for -CMR, with HRs of 1.51 (P = 0.0726), 1.61 (P = 0.0169) and 1.87 (p = 0.0005), respectively. The +CMR+S group had the highest risk of death from pump failure (HR: 5.40, p < 0.0001) and sudden cardiac death (HR: 4.40, p = 0.0218), in relation to the +CMR-S group.ConclusionsCompared with a conventional implantation approach, the use of LGE-CMR to guide LV lead deployment away from scarred myocardium results in a better clinical outcome after CRT. Pacing scarred myocardium was associated with the worst outcome, in terms of both pump failure and sudden cardiac death.

Effect of Posterolateral Left Ventricular Scar on Mortality and Morbidity following Cardiac Resynchronization Therapy

Objectives: To determine the effect of a posterolateral (PL) left ventricular scar on mortality and morbidity following cardiac resynchronization therapy (CRT).

Long-term effects of cardiac resynchronisation therapy in patients with atrial fibrillation

Objective: To compare the effects of cardiac resynchronisation therapy (CRT) in patients with heart failure (HF) in either atrial fibrillation (AF) or sinus rhythm (SR). Design: Prospective observational study. Patients: 295 consecutive patients with HF (permanent AF in 66, paroxysmal AF in 20, SR in 209; New York Heart Association (NYHA) class III or IV; left ventricular ejection fraction (LVEF) ⩽35%, QRS ⩾120 ms). Interventions: All patients underwent CRT without atrioventricular junction ablation. Main outcome measures: The primary end point was the composite of cardiovascular death or unplanned hospitalisation for major cardiovascular events. Secondary end points included the composite of cardiovascular death or hospitalisation for worsening HF. Cardiovascular mortality, total mortality and changes in NYHA class, 6-minute walking distance, quality of life (Minnesota Living with Heart Failure questionnaire) and echocardiographic variables were also considered. Results: Over a follow-up period of up to 6.8 years, no differences emerged between patients in AF or SR in any of the mortality or morbidity end points. The AF and SR groups derived similar improvements in mean NYHA class (−1.3 vs –1.2), 6-minute walking distance (92.3 vs 78.4 m) and quality of life scores (−25.2 vs –18.7) (all p<0.001). In both the AF and the SR groups, reductions were seen in left ventricular end-systolic (−25.9 vs –34.5 ml, both p<0.001) and end-diastolic (−20.2 ml, p = 0.001 vs 26.2 ml, p<0.001) volumes and improvements in LVEF (4.69% vs 7.86%, both p<0.001). Conclusions: Cardiac resynchronisation therapy leads to similar prognostic and symptomatic benefits in patients in AF and SR, even without atrioventricular junction ablation. Echocardiographic improvements are also comparable.

Left Ventricular Midwall Fibrosis as a Predictor of Mortality and Morbidity After Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy

OBJECTIVES The aim of this study was to determine whether left ventricular (LV) midwall fibrosis, detected by midwall hyperenhancement (MWHE) on late gadolinium enhancement cardiovascular magnetic resonance (CMR) imaging, predicts mortality and morbidity in patients with dilated cardiomyopathy (DCM) undergoing cardiac resynchronization therapy (CRT). BACKGROUND Midwall fibrosis predicts mortality and morbidity in patients with DCM. METHODS Patients with DCM with (+) or without (-) MWHE (n = 20 and n = 77, respectively) as well as 161 patients with ischemic cardiomyopathy (ICM) undergoing CRT (n = 258) were followed up for a maximum of 8.7 years. RESULTS Among patients with DCM, +MWHE predicted cardiovascular mortality (hazard ratio [HR]: 18.6; 95% confidence intervals [CI]: 3.51 to 98.5; p = 0.0008), total mortality or hospitalization for major adverse cardiovascular events (HR: 7.57; 95% CI: 2.71 to 21.2; p < 0.0001), and cardiovascular mortality or heart failure hospitalizations (HR: 9.56; 95% CI: 2.72 to 33.6; p = 0.0004), independent of New York Heart Association class, QRS duration, atrial fibrillation, LV volumes, LV ejection fraction, and a CMR-derived measure of dyssynchrony. Among patients with DCM and ICM, the risk of cardiovascular mortality for DCM +MWHE (adjusted HR: 18.5; 95% CI: 3.93 to 87.3; p = 0.0002) was similar to that for ICM (adjusted HR: 21.0; 95% CI: 5.06 to 87.2; p < 0.0001). Both DCM +MWHE and ICM were predictors of pump failure death as well as sudden cardiac death. LV reverse remodeling was observed in DCM -MWHE and in ICM but not in DCM +MWHE. CONCLUSIONS Midwall fibrosis is an independent predictor of mortality and morbidity in patients with DCM undergoing CRT. The outcome of DCM with midwall fibrosis is similar to that of ICM. This relationship is mediated by both pump failure and sudden cardiac death.

Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during CABG versus CABG alone

Background Studies of the transplantation of autologous bone marrow cells (BMCs) in patients with chronic ischemic heart disease have assessed effects on viable, peri-infarct tissue. We conducted a single-blinded, randomized, controlled study to investigate whether intramuscular or intracoronary administration of BMCs into nonviable scarred myocardium during CABG improves contractile function of scar segments compared with CABG alone.Methods Elective CABG patients (n = 63), with established myocardial scars diagnosed as akinetic or dyskinetic segments by dobutamine stress echocardiography and confirmed at surgery, were randomly assigned CABG alone (control) or CABG with intramuscular or intracoronary administration of BMCs. The BMCs, which were obtained at the time of surgery, were injected into the mid-depth of the scar in the intramuscular group or via the graft conduit supplying the scar in the intracoronary group. Contractile function was assessed in scar segments by dobutamine stress echocardiography before and 6 months after treatment.Results The proportion of patients showing improved wall motion in at least one scar segment after BMC treatment was not different to that observed in the control group (P = 0.092). Quantitatively, systolic fractional thickening in scar segments did not improve with BMC administration. Furthermore, BMCs did not improve scar transmurality, infarct volume, left ventricular volume, or ejection fraction.Conclusion Injection of autologous BMCs directly into the scar or into the artery supplying the scar is safe but does not improve contractility of nonviable scarred myocardium, reduce scar size, or improve left ventricular function more than CABG alone.

Cardiac resynchronization therapy delivered via a multipolar left ventricular lead is associated with reduced mortality and elimination of phrenic nerve stimulation: Long-term follow-up from a multicenter registry

Cardiac resynchronization therapy (CRT) using quadripolar left ventricular (LV) leads provides more pacing vectors compared to bipolar leads. This may avoid phrenic nerve stimulation (PNS) and allow optimal lead placement to maximize biventricular pacing. However, a long‐term improvement in patient outcome has yet to be demonstrated.

Left ventricular reverse remodelling, long-term clinical outcome, and mode of death after cardiac resynchronization therapy

To determine whether reverse left ventricular (LV) remodelling relates to long‐term outcome, major adverse cardiovascular events (MACE), mode of death, and symptomatic response after cardiac resynchronization therapy (CRT).

What is treatment success in cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is an established treatment for symptomatic patients with heart failure, a prolonged QRS duration, and impaired left ventricular (LV) function. Identification of ‘responders’ and ‘non-responders’ to CRT has attracted considerable attention. The response to CRT can be measured in terms of symptomatic response or clinical outcome, or both. Alternatively, the response to CRT can be measured in terms of changes in surrogate measures of outcome, such as LV volumes, LV ejection fraction, invasive measures of cardiac performance, peak oxygen uptake, and neurohormones. This review explores whether these measures can be used in assessing the symptomatic and prognostic response to CRT. The role of these parameters to the management of individual patients is also discussed.

Long-term effects of upgrading from right ventricular pacing to cardiac resynchronization therapy in patients with heart failure.

AIMS To determine the effects of upgrading from right ventricular (RV) pacing to cardiac resynchronization therapy (CRT) in patients with heart failure. METHODS AND RESULTS Patients with heart failure [age 67.3 +/- 9.6 years (mean +/- SD), NYHA class III or IV, left ventricular ejection fraction (LVEF) <or= 35%, QRS >or= 120 ms] underwent de novo CRT (n = 336) or upgrading from RV pacing [n = 58; VVIR in 24, DDDR in 34] to CRT. The endpoint of death from any cause or major cardiovascular events, cardiovascular death or hospitalization for heart failure, and cardiovascular death or death from any cause was determined after a maximum follow-up of 7.7 years. No differences emerged between the de novo CRT and the upgrade-to-CRT groups with respect to any of the clinical endpoints. The de novo CRT and upgrade-to-CRT groups derived similar improvements in NYHA class [-1.2 vs. -1.3 (mean), both P < 0.0001), 6 min walking distance [75.9 (P < 0.0001) vs. 46.4 (P = 0.0205) m], and quality of life scores [-25.2 vs. -18.7 (both P < 0.0001)] 1 year after implantation. Response rates using a combined clinical score (>or=1 NYHA classes or >or=25% increase in 6 min walking distance plus survival with freedom from heart failure hospitalizations for 1 year) were 73.2% and 75.4%, respectively (P = NS). There were reductions in left ventricular end-systolic volume [median of 20.3 mL (P = 0.0012) and 22.7 mL (P = 0.0066), respectively] and improvements in LVEF [median of 2.9% and 9.3%, respectively (both P < 0.0001)]. CONCLUSION In patients with heart failure who are RV-paced, upgrading to CRT is associated with a similar long-term risk of mortality and morbidity to patients undergoing de novo CRT. Symptomatic improvements and degree of reverse remodelling are also comparable.

Cardiac resynchronisation therapy in patients with heart failure and a normal QRS duration: the RESPOND study

Objectives To evaluate the clinical response to cardiac resynchronisation therapy (CRT) in patients with heart failure and a normal QRS duration (<120 ms). Setting Single centre. Patients 60 patients with heart failure and a normal QRS duration receiving optimal pharmacological treatment (OPT). Interventions Patients were randomly assigned to CRT (n=29) or to a control group (OPT, n=31). Cardiovascular magnetic resonance was used in order to avoid scar at the site of left ventricular (LV) lead deployment. Main outcome measures The primary end point was a change in 6 min walking distance (6-MWD). Other measures included a change in quality of life scores (Minnesota Living with Heart Failure questionnaire) and New York Heart Association class. Results In 93% of implantations, the LV lead was deployed over non-scarred myocardium. At 6 months, the 6-MWD increased with CRT compared with OPT (p<0.0001), with more patients reaching a ≥25% increase (51.7% vs 12.9%, p=0.0019). Compared with OPT, CRT led to an improvement in quality-of-life scores (p=0.0265) and a reduction in NYHA class (p<0.0001). The composite clinical score (survival for 6 months free of heart failure hospitalisations plus improvement by one or more NYHA class or by ≥25% in 6-MWD) was better in CRT than in OPT (83% vs 23%, respectively; p<0.0001). Although no differences in total or cardiovascular mortality emerged between OPT and CRT, patients receiving OPT had a higher risk of death from pump failure than patients assigned to CRT (HR=8.41, p=0.0447) after a median follow-up of 677.5 days. Conclusions CRT leads to an improvement in symptoms, exercise capacity and quality of life in patients with heart failure and a normal QRS duration. (ClinicalTrials.gov number, NCT00480051.)