Intravenous iron for heart failure, iron deficiency definitions, and clinical response: the IRONMAN trial.

BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure? METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100 µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death. RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT < 20%, especially when ferritin was ≥100 µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant. CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT < 20% with ferritin > 100 µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.

Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics.

BACKGROUND AND AIMS: To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide. METHODS AND RESULTS: A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h). The primary endpoint was a diuretic effect, assessed by change in weight (kg). Secondary endpoints included a change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 h was 977 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 h was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; P = 0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) vs. 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; P = 0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments. CONCLUSION: In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04860011.

Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial.

BACKGROUND: For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure. METHODS: IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK. Patients aged 18 years or older with heart failure (left ventricular ejection fraction ≤45%) and transferrin saturation less than 20% or serum ferritin less than 100 µg/L were eligible. Participants were randomly assigned (1:1) using a web-based system to intravenous ferric derisomaltose or usual care, stratified by recruitment context and trial site. The trial was open label, with masked adjudication of the outcomes. Intravenous ferric derisomaltose dose was determined by patient bodyweight and haemoglobin concentration. The primary outcome was recurrent hospital admissions for heart failure and cardiovascular death, assessed in all validly randomly assigned patients. Safety was assessed in all patients assigned to ferric derisomaltose who received at least one infusion and all patients assigned to usual care. A COVID-19 sensitivity analysis censoring follow-up on Sept 30, 2020, was prespecified. IRONMAN is registered with ClinicalTrials.gov, NCT02642562. FINDINGS: Between Aug 25, 2016, and Oct 15, 2021, 1869 patients were screened for eligibility, of whom 1137 were randomly assigned to receive intravenous ferric derisomaltose (n=569) or usual care (n=568). Median follow-up was 2·7 years (IQR 1·8-3·6). 336 primary endpoints (22·4 per 100 patient-years) occurred in the ferric derisomaltose group and 411 (27·5 per 100 patient-years) occurred in the usual care group (rate ratio [RR] 0·82 [95% CI 0·66 to 1·02]; p=0·070). In the COVID-19 analysis, 210 primary endpoints (22·3 per 100 patient-years) occurred in the ferric derisomaltose group compared with 280 (29·3 per 100 patient-years) in the usual care group (RR 0·76 [95% CI 0·58 to 1·00]; p=0·047). No between-group differences in deaths or hospitalisations due to infections were observed. Fewer patients in the ferric derisomaltose group had cardiac serious adverse events (200 [36%]) than in the usual care group (243 [43%]; difference -7·00% [95% CI -12·69 to -1·32]; p=0·016). INTERPRETATION: For a broad range of patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric derisomaltose administration was associated with a lower risk of hospital admissions for heart failure and cardiovascular death, further supporting the benefit of iron repletion in this population. FUNDING: British Heart Foundation and Pharmacosmos.

Renal function and the long-term clinical outcomes of cardiac resynchronization therapy with or without defibrillation.

BACKGROUND AND AIMS: Patients with moderate-to-severe chronic kidney disease (CKD) are underrepresented in clinical trials of cardiac resynchronization therapy (CRT)-defibrillation (CRT-D) or CRT-pacing (CRT-P). We sought to determine whether outcomes after CRT-D are better than after CRT-P over a wide spectrum of CKD. METHODS AND RESULTS: Clinical events were quantified in relation to preimplant estimated glomerular filtration rate (eGFR) after CRT-D (n = 410 [39.2%]) or CRT-P (n = 636 [60.8%]) implantation. Over a follow-up period of 3.7 years (median, interquartile range: 2.1-5.7), the eGFR < 60 group (n = 598) had a higher risk of total mortality (adjusted hazard ratio [aHR]: 1.28; P = 0.017), total mortality or heart failure (HF) hospitalization (aHR: 1.32; P = 0.004), total mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.34; P = 0.002), and cardiac mortality (aHR: 1.33; P = 0.036), compared to the eGFR ≥ 60 group (n = 448), after covariate adjustment. In analyses of CRT-D versus CRT-P, CRT-D was associated with a lower risk of total mortality (eGFR ≥ 60 HR: 0.65; P = 0.028; eGFR < 60 HR: 0.64, P = 0.002), total mortality or HF hospitalization (eGFR ≥ 60 aHR: 0.66; P = 0.021; eGFR < 60 aHR: 0.69, P = 0.007), total mortality or hospitalization for MACEs (eGFR ≥ 60 aHR: 0.70; P = 0.039; eGFR < 60 aHR: 0.69, P = 0.005), and cardiac mortality (eGFR ≥ 60 aHR: 0.60; P = 0.026; eGFR < 60 aHR: 0.55; P = 0.003). CONCLUSION: In CRT recipients, moderate CKD is associated with a higher mortality and morbidity compared to normal renal function or mild CKD. Despite less favorable absolute outcomes, patients with moderate CKD had better outcomes after CRT-D than after CRT-P.

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.

INTRODUCTION: 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. METHODS: A total of 721 consecutive patients with conventional CRTD criteria implanted with quadripolar (n = 357) or bipolar (n = 364) LV leads were enrolled into a registry at 3 UK centers. Lead performance and mortality was analyzed over a 5-year period. RESULTS: Patients receiving a quadripolar lead were of similar age and sex to those receiving a bipolar lead, although a lower proportion had ischemic heart disease (62.6% vs. 54.1%, P = 0.02). Both groups had similar rates of procedural success, although lead threshold, impedance, and procedural radiation dose were significantly lower in those receiving a quadripolar lead. PNS was more common in those with quadripolar leads (16.0% vs. 11.6%, P = 0.08), but was eliminated by switching pacing vector in all cases compared with 60% in the bipolar group (P < 0.001). Furthermore, LV lead displacement (1.7% vs. 4.6%, P = 0.03) and repositioning (2.0% vs. 5.2%, P = 0.03) occurred significantly less often in those with a quadripolar lead. All-cause mortality was also significantly lower in the quadripolar compared to bipolar lead group in univariate and multivariate analysis (13.2% vs. 22.5%, P < 0.001). CONCLUSIONS: In a large, multicenter experience, the use of quadripolar LV leads for CRT was associated with elimination of PNS and lower overall mortality. This has important implications for LV pacing lead choice.

Current and future role of cardiovascular magnetic resonance in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) has revolutionized the treatment of selected patients with systolic heart failure. It is well recognized, however, that the symptomatic response to and the outcome of CRT is highly variable. The degree of pre-implant mechanical dyssynchrony and the extent as well as the localization of myocardial scarring are known to contribute to this variability. Cardiovascular magnetic resonance (CMR) is the gold-standard imaging modality for the assessment of myocardial structure and function. Recently, CMR has also been shown to be useful in assessing cardiac dyssynchrony and in guiding left ventricular lead deployment away from scarred myocardium. This review explores the current role of CMR in risk stratification and in guiding LV lead deployment. The potential of CMR in identifying the arrhythmogenic substrate is also discussed.

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

BACKGROUND: Myocardial 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). METHODS: 559 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). RESULTS: Over 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. CONCLUSIONS: Compared 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.

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.

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). SETTING: Cardiac device therapy center. PATIENTS: Five hundred and fifty-six patients (age 70.4 ± 10.7 years [mean ± standard deviation]). INTERVENTIONS: CRT-pacing or CRT-defibrillation device implantation. MAIN OUTCOME MEASURES: Cardiovascular mortality and events over a maximum follow-up period of 9.1 years. RESULTS: Hazard ratios (HRs [95% 785]797) for cardiovascular mortality, adjusted for age, gender, QRS duration, heart failure etiology, New York Heart Association class, and presence of diabetes and atrial fibrillation, were derived for LV lead tip positions in terms of veins, circumferential, and longitudinal positions with respect to the LV chamber. For vein position, these were 1.07 (0.74-1.56) for anterolateral vein position and 1.24 (0.79-1.95) for the middle cardiac vein, compared with a posterolateral vein. For circumferential lead tip position, HRs were 1.56 (0.73-3.34) for anterolateral and 1.57 (0.76-3.25) for lateral, compared with posterior positions. For longitudinal lead tip positions, HRs were 1.02 (0.72-1.46) for basal and 1.21 (0.68-2.17) for apical, compared with mid-ventricular positions. The risk of meeting the composite endpoints of cardiovascular death or hospitalizations for heart failure and death from any cause or hospitalizations for major adverse cardiovascular events was similar among the various LV lead tip positions. CONCLUSIONS: The position of the LV lead over the LV free wall, assessed by fluoroscopy, has no influence over the long-term outcome of CRT.

Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.

AIMS: The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) predicts mortality and morbidity after cardiac resynchronization therapy (CRT). Growth differentiation factor-15, a transforming growth factor-beta-related cytokine which is up-regulated in cardiomyocytes via multiple stress pathways, predicts mortality in patients with heart failure treated pharmacologically. METHODS AND RESULTS: Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 +/- 11 years (mean +/- SD), left ventricular ejection fraction (LVEF) 23.1 +/- 9.8%, New York Class Association (NYHA) class III (n = 117) or IV (n = 41), and QRS 153.9 +/- 28.2 ms] undergoing CRT and followed up for a maximum of 5.4 years for events. In a stepwise Cox proportional hazards model with bootstrapping, adopting log GDF-15, log NT pro-BNP, LVEF, and NYHA class as independent variables, only log GDF-15 [hazard ratio (HR), 3.76; P = 0.0049] and log NT pro-BNP (HR, 2.12; P = 0.0171) remained in the final model. In the latter, the bias-corrected slope was 0.85, the optimism (O) was -0.06, and the c-statistic was 0.74, indicating excellent internal validity. In univariate analyses, log GDF-15 [HR, 5.31; 95% confidence interval (CI), 2.31-11.9; likelihood ratio (LR) chi(2) = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55-5.26; LR chi(2) = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91-17.5; LR chi(2) = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR chi(2) for all endpoints. CONCLUSION: Pre-implant GDF-15 is a strong predictor of mortality and morbidity after CRT, independent of NT pro-BNP. The predictive value of these analytes is enhanced by combined measurement.

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

BACKGROUND: Intuitively, cardiac dyssynchrony is the inevitable result of myocardial injury. We hypothesized 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. METHODS: 225 patients with heart failure, grouped according to QRS duration of <120 ms (A, n = 75), between 120-149 ms (B, n = 75) or >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). RESULTS: Compared 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). CONCLUSION: Radial 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.

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= 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.

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

BACKGROUND: It 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. METHODS: Forty 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. RESULTS: At 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). CONCLUSION: Left 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.

Implantable cardioverter defibrillator therapy for primary prevention of sudden cardiac death after myocardial infarction: implications of international guidelines.

STUDY OBJECTIVE: To estimate the proportion of patients eligible for implantable cardioverter defibrillator (ICD) therapy for the primary prevention of sudden cardiac death after a myocardial infarction (MI), according to the current guidelines. METHODS: Eligibility was assessed retrospectively at 6 weeks in 513 post-MI survivors (age 66 +/- 13 years, left ventricular ejection fraction 48.2 +/- 17%) on the basis of an electrocardiogram and an echocardiogram. RESULTS: LVEF was < or = 40% in 37% and < or = 35% in 30%, and QRS duration was <120 ms in 89% and > or =120 ms in 11% of patients. The proportion of post-MI patients meeting the criteria set by guidelines were 37% for 2006 American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) 26.5% for 2008 ACC/AHA/Canadian Heart Rhythm Society 16.3% for 2005 US Centers for Medicare and Medicaid Services (CMS), and 5.8% for the 2006 United Kingdom (UK) National Institute of Clinical Excellence (NICE). According to 2005 CMS and 2006 UK-NICE guidelines, Holter monitoring was required in 7% and 18%, respectively. For the United States (700,000 MI in 2006), the 2006 ACC/AHA/ESC guidelines equate to 216,783 ICD implantations/year. For UK (60,499 MI in 2006), the 2006 NICE guidelines equate to 2,941 ICD implantations, 10,488 Holter studies, and 1,065 VT induction tests/year. CONCLUSIONS: Current ICD therapy guidelines for primary prevention of SCD post-MI demand a substantial increase in service provision worldwide.

Cardiac resynchronization therapy in patients with mildly impaired left ventricular function.

AIMS: We sought to determine the unknown effects of cardiac resynchronization therapy (CRT) in patients with a left ventricular ejection fraction (LVEF) >35%. Because of its technical limitations, echocardiography (Echo) may underestimate LVEF, compared with cardiovascular magnetic resonance (CMR). METHODS: Of 157 patients undergoing CRT (New York Heart Association [NYHA] functional class III or IV, QRS > or = 120 ms), all of whom had a preimplant Echo-LVEF < or =35%, 130 had a CMR-LVEF < or =35% (Group A, 19.7 +/- 7.0%[mean +/- standard deviation]) and 27 had a CMR-LVEF >35% (Group B, 43.6 +/- 7.7%). All patients underwent a CMR scan at baseline and a clinical evaluation, including a 6-minute walk test and a quality of life questionnaire, at baseline and after CRT. RESULTS: Both groups derived similar improvements in NYHA functional class (A =-1.3, B =-1.2, [mean]), quality of life scores (A =-21.6, B =-33.0; all P < 0.0001 for changes from baseline), and 6-minute walking distance (A = 64.5, B = 70.1 m; P < 0.001 and P < 0.0001, respectively). Symptomatic response rates (increase by > or =1 NYHA classes or 25% 6-minute walking distance) were 79% in group A and 92% in group B. Over a maximum follow-up period of 5.9 years for events, patients in group A were at a higher risk of death from any cause, hospitalization for major cardiovascular events (P = 0.0232), or cardiovascular death (P = 0.0411). There were borderline differences in the risk of death from any cause (P = 0.0664) and cardiovascular death or hospitalization for heart failure (P = 0.0526). CONCLUSIONS: This observational study suggests that the benefits of CRT extend to patients with a LVEF > 35%.

Life threatening polyserositis post oesophagectomy.

A 46 year old lady presented three weeks after an oesophagectomy for oesophageal carcinoma with increasing breathlessness and a large left-sided pleural effusion. Computed tomography (CT) scan of her thorax, abdomen and pelvis revealed a large left-sided and small right-sided pleural effusions, a pericardial effusion, ascites and intra-abdominal lymphadenopathy. The patient underwent both pericardial and pleural fluid drainage, however, unfortunately, deteriorated despite these interventions with increasing oxygen requirements requiring nasal high flow oxygen on the Intensive Care Unit. Her pleural and pericardial collections resolved with colchicine and later introduction of prednisolone over a period of 5 weeks. Polyserositis is well recognised after cardiac surgery, but such a dramatic complication after thoracotomy for non-cardiac surgery has as not previously been reported. The polyserositis may relate to the induction chemotherapy combined with surgery.

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.

Long-Term Outcomes of Cardiac Resynchronization Therapy Using Apical Versus Nonapical Left Ventricular Pacing.

Background Experimental evidence indicates that left ventricular ( LV ) apical pacing is hemodynamically superior to nonapical LV pacing. Some studies have shown that an LV apical lead position is unfavorable in cardiac resynchronization therapy. We sought to determine whether an apical LV lead position influences cardiac mortality after cardiac resynchronization therapy. Methods and Results In this retrospective observational study, the primary end point of cardiac mortality was assessed in relation to longitudinal (basal, midventricular, or apical) and circumferential (anterior, lateral, or posterior) LV lead positions, as well as right ventricular (apical or septal), assigned using fluoroscopy. Lead positions were assessed in 1189 patients undergoing cardiac resynchronization therapy implantation over 15 years. After a median follow-up of 6.0 years (interquartile range: 4.4-7.7 years), an apical LV lead position was associated with lower cardiac mortality than a nonapical position (adjusted hazard ratio: 0.74; 95% confidence interval, 0.56-0.99) after covariate adjustment. There were no differences in total mortality or heart failure hospitalization. Death from pump failure was lower with apical than nonapical positions (adjusted hazard ratio: 0.69; 95% confidence interval, 0.51-0.94). Compared with a basal position, an apical LV position was also associated with lower risk of sudden cardiac death (adjusted hazard ratio: 0.34; 95% confidence interval, 0.13-0.93). No differences emerged between circumferential LV lead positions or right ventricular positions with respect to any end point. Conclusions In recipients of cardiac resynchronization therapy, an apical LV lead position was associated with better long-term cardiac survival than a nonapical position. This effect was due to a lower risk of pump failure and sudden cardiac death.

Late gadolinium enhancement-cardiovascular magnetic resonance as a predictor of response to cardiac resynchronization therapy in patients with ischaemic cardiomyopathy.

AIM: To determine whether myocardial scarring, quantified using late gadolinium enhancement-cardiovascular magnetic resonance (LGE-CMR), predicts response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: A total of 45 patients with ischaemic cardiomyopathy [age 67.1 +/- 10.4 years (mean +/- SD)] underwent assessment of 6 min walking distance (6MWD) and quality of life (QoL) before and after CRT. Scar size (percentage of left ventricular mass), location, and transmurality were assessed prior to CRT using LGE-CMR. Responders (survived for 1 year with no heart failure hospitalizations, and improvement by >or=1 NYHA classes or >or=25% 6MWD) had a higher left ventricular ejection fraction (P = 0.048), smaller scars (<33%) (P = 0.009), and fewer scars with >or=51% transmurality (P = 0.002). Scar size correlated negatively with change in 6MWD (r = -0.54, P < 0.001) and positively with changes in QoL scores (r = 0.35, P = 0.028). Responder rates in patients with <33% scar were higher than in those with >or=33% scar (82 vs. 35%, P < 0.01). Responder rates in patients with scar transmurality <51% were higher than in those with >or=51% (89 vs. 46%, P < 0.01). Among the patients with posterolateral scars, a transmurality value of >or=51% was associated with a particularly poor response rate (23%), compared with scars with <51% transmurality (88%, P < 0.001). In multivariate analyses, both scar size (P = 0.022) and transmurality (P = 0.004) emerged as predictors of response. In patients with posterolateral scars, pacing outside the scar was associated with a better responder rate than pacing over the scar (86 vs. 33%, P = 0.004). CONCLUSIONS: In patients with ischaemic cardiomyopathy, a scar size >or=33%, a transmurality >or=51%, and pacing over a posterolateral scar are associated with a suboptimal response to CRT.