Russell E.A. Smith

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, pu200a=u200a0.001 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

OBJECTIVESnThe 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).nnnBACKGROUNDnMidwall fibrosis predicts mortality and morbidity in patients with DCM.nnnMETHODSnPatients 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.nnnRESULTSnAmong 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.nnnCONCLUSIONSnMidwall 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.

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).

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

AIMSnTo determine the effects of upgrading from right ventricular (RV) pacing to cardiac resynchronization therapy (CRT) in patients with heart failure.nnnMETHODS AND RESULTSnPatients 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)].nnnCONCLUSIONnIn 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 (<120u2005ms). Setting Single centre. Patients 60u2005patients 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 6u2005min 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 6u2005months, 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 6u2005months 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 677.5u2005days. 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.)

Development and validation of a clinical index to predict survival after cardiac resynchronisation therapy

Objective: To develop and validate a prognostic risk index of cardiovascular mortality after cardiac resynchronisation therapy (CRT). Design: Prospective cohort study. Setting: District general hospital. Patients: 148 patients with heart failure (mean age 66.7 (SD 10.4) years), New York Heart Association class III or IV, LVEF <35%) who underwent CRT. Interventions: CRT device implantation. Main outcome measures: Value of a composite index in predicting cardiovascular mortality, validated internally by bootstrapping. The predictive value of the index was compared to factors that are known to predict mortality in patients with heart failure. Results: All patients underwent assessment of 16 prognostic risk factors, including cardiovascular magnetic resonance (CMR) measures of myocardial scarring (gadolinium-hyperenhancement) and dyssynchrony, before implantation. Clinical events were assessed after a median follow-up of 913 (interquartile range 967) days. At follow-up, 37/148 (25%) of patients died from cardiovascular causes. In Cox proportional hazards analyses, (DSC) Dyssynchrony, posterolateral Scar location (both p<0.0001) and Creatinine (pu200a=u200a0.0046) emerged as independent predictors of cardiovascular mortality. The DSC index, derived from these variables combined, emerged as a powerful predictor of cardiovascular mortality. Compared to patients with a DSC <3, cardiovascular mortality in patients in the intermediate DSC index (3–5; HR: 11.1 (95% confidence interval (CI) 3.00 to 41.1), pu200a=u200a0.0003) and high DSC index (⩾5; HR: 30.5 (95% CI 9.15 to 101.8), p<0.0001) were higher. Bootstrap validation confirmed excellent calibration and internal validity of the prediction model. Conclusion: The DSC index, derived from a standard CMR scan and plasma creatinine before implantation, is a powerful predictor of cardiovascular mortality after CRT.

Long-term effects of cardiac resynchronization therapy in octogenarians: a comparative study with a younger population

AIMSnHeart failure is a disease of octogenarians. The evidence base for cardiac resynchronization therapy (CRT) has emerged from trials of patients in their 60s. We compared the effectiveness of CRT in octogenerians with younger patients.nnnMETHODS AND RESULTSnPatients aged >or=80 years [n = 53, age 83.7 +/- 2.6 years (mean +/- SD)] and <80 years (n = 277, age 66.9 +/- 9.5 years) with ischaemic or non-ischaemic cardiomyopathy (NYHA class III or IV heart failure, left ventricular ejection fraction <35%, QRS >or= 120 ms) underwent CRT. A clinical assessment, including a 6-min walk test, and a quality of life assessment (Minnesota Living with Heart Failure questionnaire) were undertaken at baseline and after CRT. In octogenarians, CRT was associated with similar changes in NYHA class [-1.28 vs. -1.22, P < 0.0001 (P-values refer to changes from baseline)], 6-min walking distance (77.2 vs. 78.6 m, P < 0.0001), and quality of life scores (-20.4 vs. -31.4, P = 0.0084) to <80 year olds. A symptomatic response to CRT (improvement by >or=1 NYHA classes or >or=25% 6-min walking distance) was observed in 80% of <80 year olds and in 81% of octogenarians (P = NS). Using a combined clinical score (CCS; survival for 1 year with no heart failure hospitalizations, and; improvement by >or=1 NYHA classes or >or=25% 6-min walking distance), a response was observed in 201 out of 277 (73%) patients <80 years and in 36 out of 53 (68%) octogenarians (P = NS). After a maximum follow-up of 7.6 years (median 634 days), no group differences emerged with respect to the composite endpoints of cardiovascular death or hospitalization for major cardiovascular events, the composite endpoint of cardiovascular death or heart failure hospitalization, cardiovascular mortality, or total mortality.nnnCONCLUSIONnOctogenarians derive similar benefits from CRT to younger patients.

Radial dyssynchrony assessed by cardiovascular magnetic resonance in relation to left ventricular function, myocardial scarring and QRS duration in patients with heart failure

BackgroundIntuitively, cardiac dyssynchrony is the inevitable result of myocardial injury. We hypothezised that radial dyssynchrony reflects left ventricular remodeling, myocardial scarring, QRS duration and impaired LV function and that, accordingly, it is detectable in all patients with heart failure.Methods225 patients with heart failure, grouped according to QRS duration of <120 ms (A, n = 75), between 120-149 ms (B, n = 75) or ≥150 ms (C, n = 75), and 50 healthy controls underwent assessment of radial dyssynchrony using the cardiovascular magnetic resonance tissue synchronization index (CMR-TSI = SD of time to peak inward endocardial motion in up to 60 myocardial segments).ResultsCompared to 50 healthy controls (21.8 ± 6.3 ms [mean ± SD]), CMR-TSI was higher in A (74.8 ± 34.6 ms), B (92.4 ± 39.5 ms) and C (104.6 ± 45.6 ms) (all p < 0.0001). Adopting a cut-off CMR-TSI of 34.4 ms (21.8 plus 2xSD for controls) for the definition of dyssynchrony, it was present in 91% in A, 95% in B and 99% in C. Amongst patients in NYHA class III or IV, with a LVEF<35% and a QRS>120 ms, 99% had dyssynchrony. Amongst those with a QRS<120 ms, 91% had dyssynchrony. Across the study sample, CMR-TSI was related positively to left ventricular volumes (p < 0.0001) and inversely to LVEF (CMR-TSI = 178.3 e (-0.033 LVEF) ms, p < 0.0001).ConclusionRadial dyssynchrony is almost universal in patients with heart failure. This vies against the notion that a lack of response to CRT is related to a lack of dyssynchrony.