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.

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 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.

Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Recent studies have cast doubt on the benefit of cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) versus pacing (CRT-P) for patients with nonischemic cardiomyopathy (NICM). Left ventricular myocardial scar portends poor clinical outcomes. OBJECTIVES: The aim of this study was to determine whether CRT-D is superior to CRT-P in patients with NICM either with (+) or without (-) left ventricular midwall fibrosis (MWF), detected by cardiac magnetic resonance. METHODS: Clinical events were quantified in patients with NICM who were +MWF (n = 68) or -MWF (n = 184) who underwent cardiac magnetic resonance prior to CRT device implantation. RESULTS: In the total study population, +MWF emerged as an independent predictor of total mortality (adjusted hazard ratio [aHR]: 2.31; 95% confidence interval [CI]: 1.45 to 3.68), total mortality or heart failure hospitalization (aHR: 2.02; 95% CI: 1.32 to 3.09), total mortality or hospitalization for major adverse cardiac events (aHR: 2.02; 95% CI: 1.32 to 3.07), death from pump failure (aHR: 1.95; 95% CI: 1.11 to 3.41), and sudden cardiac death (aHR: 3.75; 95% CI: 1.26 to 11.2) over a maximum follow-up period of 14 years (median 3.8 years [interquartile range: 2.0 to 6.1 years] for +MWF and 4.6 years [interquartile range: 2.4 to 8.3 years] for -MWF). In separate analyses of +MWF and -MWF, total mortality (aHR: 0.23; 95% CI: 0.07 to 0.75), total mortality or heart failure hospitalization (aHR: 0.32; 95% CI: 0.12 to 0.82), and total mortality or hospitalization for major adverse cardiac events (aHR: 0.30; 95% CI: 0.12 to 0.78) were lower after CRT-D than after CRT-P in +MWF but not in -MWF. CONCLUSIONS: In patients with NICM, CRT-D was superior to CRT-P in +MWF but not -MWF. These findings have implications for the choice of device therapy in patients with NICM.

Cost-Effectiveness Analysis of Quadripolar Versus Bipolar Left Ventricular Leads for Cardiac Resynchronization Defibrillator Therapy in a Large, Multicenter UK Registry.

OBJECTIVES: The objective of this study was to evaluate the cost-effectiveness of quadripolar versus bipolar cardiac resynchronization defibrillator therapy systems. BACKGROUND: Quadripolar left ventricular (LV) leads for cardiac resynchronization therapy reduce phrenic nerve stimulation (PNS) and are associated with reduced mortality compared with bipolar leads. METHODS: A total of 606 patients received implants at 3 UK centers (319 Q, 287 B), between 2009 and 2014; mean follow-up was 879 days. Rehospitalization episodes were costed at National Health Service national tariff rates, and EQ-5D utility values were applied to heart failure admissions, acute coronary syndrome events, and mortality data, which were used to estimate quality-adjusted life-year differences over 5 years. RESULTS: Groups were matched with regard to age and sex. Patients with quadripolar implants had a lower rate of hospitalization than those with bipolar implants (42.6% vs. 55.4%; p = 0.002). This was primarily driven by fewer hospital readmissions for heart failure (51 [16%] vs. 75 [26.1%], respectively, for quadripolar vs. bipolar implants; p = 0.003) and generator replacements (9 [2.8%] vs. 19 [6.6%], respectively; p = 0.03). Hospitalization for suspected acute coronary syndrome, arrhythmia, device explantation, and lead revisions were similar. This lower health-care utilization cost translated into a cumulative 5-year cost saving for patients with quadripolar systems where the acquisition cost was <£932 (US $1,398) compared with bipolar systems. Probabilistic sensitivity analysis results mirrored the deterministic calculations. For the average additional price of £1,200 (US $1,800) over a bipolar system, the incremental cost-effective ratio was £3,692 per quality-adjusted life-year gained (US $5,538), far below the usual willingness-to-pay threshold of £20,000 (US $30,000). CONCLUSIONS: In a UK health-care 5-year time horizon, the additional purchase price of quadripolar cardiac resynchronization defibrillator therapy systems is largely offset by lower subsequent event costs up to 5 years after implantation, which makes this technology highly cost-effective compared with bipolar systems.

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.

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.

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.

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.

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.).

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.

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.

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

AIMS: 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). METHODS AND RESULTS: Three hundred and twenty-two patients with heart failure (HF) [age 69.2 ± 10.7 years (mean ± standard deviation)] underwent a clinical assessment and echocardiography before and at a maximum of 9.1 years (median: 36.2 months) after CRT device implantation. Left ventricular reverse remodelling (≥15% reduction in LV end-systolic volume) predicted survival from cardiovascular death (HR: 0.57, P = 0.0066), death from any cause (HR: 0.59, P = 0.0064), death from any cause/hospitalizations for MACE (HR: 0.67, P = 0.0158), and death from pump failure (HR: 0.45, P = 0.0024), independent of beta-blocker use, HF aetiology, gender, baseline NYHA class, and atrial rhythm. Left ventricular reverse remodelling did not predict sudden cardiac death. At 1 year, the symptomatic response rate (improvement by ≥1 NYHA classes or ≥25% increase in walking distance) was 86% in survivors and 76% in non-survivors (P = NS). Left ventricular reverse remodelling did not predict symptomatic response and the symptomatic response did not predict clinical outcome. CONCLUSION: Left ventricular reverse remodelling is an independent predictor of clinical outcome for up to 5 years after CRT device implantation. Pump failure, rather than sudden cardiac death, is primarily responsible for this association. Left ventricular reverse remodelling, however, does not predict a symptomatic response. There is discordance between the symptomatic response to and the survival benefit of CRT.