Shajil Chalil

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.

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.

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.

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.

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

AIMS Heart 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. METHODS AND RESULTS Patients 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. CONCLUSION Octogenarians derive similar benefits from CRT to younger patients.

Fluoroscopic left ventricular lead position and the long-term clinical outcome of cardiac resynchronization therapy.

Background:  To determine the effects of left ventricular (LV) lead tip position on the long‐term outcome of cardiac resynchronization therapy (CRT).

Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging

BackgroundIt is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction.MethodsForty two patients, aged 48.7 ± 2.3 yrs (mean ± SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients.ResultsAt presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001).ConclusionLeft ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction.

Modelling the economic and health consequences of cardiac resynchronization therapy in the UK

ABSTRACT Objective: Clinical evidence supports the use of cardiac resynchronization therapy (CRT) in advanced heart failure, but its cost-effectiveness is still unclear. This analysis assessed the economic and health consequences in the UK of implanting a CRT in patients with NYHA class III-IV heart failure. Methods: A discrete event simulation of heart failure was used to compare the course over 5 years of 1000 identical pairs of patients – one receiving both CRT and optimum pharmacologic treatment (OPT), the other OPT alone. All inputs were obtained from the data collected in the CArdiac REsynchronization in Heart Failure (CARE-HF) trial and a hospital in the UK. Direct medical costs (in 2004 £) from the perspective of the National Health Service were considered. Both costs and benefits were discounted at 3.5%. Sensitivity analyses addressed all model inputs and multivariate analyses were performed by varying key parameters simultaneously. Results: The model predicted 471 deaths and 2263 hospitalizations over 5 years with OPT alone and 348 deaths and 1764 hospitalizations with CRT, equivalent to a 26% reduction in mortality and 22% in hospitalizations, at a discounted cost of £11 423 per patient with CRT vs. £4900 with OPT alone. CRT was predicted to increase quality-adjusted survival by 0.43 QALYs per patient, resulting in an incremental cost-effectiveness ratio of £15 247 per QALY gained (range: £12 531–£23 184). Sensitivity analyses revealed that this outcome was most sensitive to time horizon and cost of implantation. Conclusion: Based on these 5‐year analyses, CRT is expected to yield substantial health benefits at a reasonable cost.