Timing of cardiac resynchronization therapy implantation.

AIMS: The optimum timing of cardiac resynchronization therapy (CRT) implantation is unknown. We explored long-term outcomes after CRT in relation to the time interval from a first heart failure hospitalization (HFH) to device implantation. METHODS AND RESULTS: A database covering the population of England (56.3 million in 2019) was used to quantify clinical outcomes after CRT implantation in relation to first HFHs. From 2010 to 2019, 64 968 patients [age: 71.4 ± 11.7 years; 48 606 (74.8%) male] underwent CRT implantation, 57% in the absence of a previous HFH, 12.9% during the first HFH, and 30.1% after ≥1 HFH. Over 4.54 (2.80-6.71) years [median (interquartile range); 272 989 person-years], the time in years from the first HFH to CRT implantation was associated with a higher risk of total mortality [hazard ratio (HR); 95% confidence intervals (95% CI)] (1.15; 95% CI 1.14-1.16, HFH (HR: 1.26; 95% CI 1.24-1.28), and the combined endpoint of total mortality or HFH (HR: 1.19; 95% CI 1.27-1.20) than CRT in patients with no previous HFHs, after co-variate adjustment. Total mortality (HR: 1.67), HFH (HR: 2.63), and total mortality or HFH (HR: 1.92) (all P < 0.001) were highest in patients undergoing CRT ≥2 years after the first HFH. CONCLUSION: In this study of a healthcare system covering an entire nation, delays from a first HFH to CRT implantation were associated with progressively worse long-term clinical outcomes. The best clinical outcomes were observed in patients with no previous HFH and in those undergoing CRT implantation during the first HFH. CONDENSED ABSTRACT: The optimum timing of CRT implantation is unknown. In this study of 64 968 consecutive patients, delays from a first heart failure hospitalization (HFH) to CRT implantation were associated with progressively worse long-term clinical outcomes. Each year from a first HFH to CRT implantation was associated with a 21% higher risk of total mortality and a 34% higher risk of HFH. The best outcomes after CRT were observed in patients with no previous HFHs and in those undergoing implantation during their first HFH.

Improved prognosis after cardiac resynchronization therapy over a decade.

AIMS: The past decade has seen an increased delivery of cardiac resynchronization therapy (CRT) for patients with heart failure (HF). We explored whether clinical outcomes after CRT have changed from the perspective of an entire public healthcare system. METHODS AND RESULTS: A national database covering the population of England (56.3 million in 2019) was used to explore clinical outcomes after CRT from 2010 to 2019. A total of 64 698 consecutive patients (age 71.4 ± 11.7 years; 74.8% male) underwent CRT-defibrillation [n = 32 313 (49.7%)] or CRT-pacing [n = 32 655 (50.3%)] implantation. From 2010-2011 to 2018-2019, there was a 76% increase in CRT implantations. During the same period, the proportion of patients with hypertension (59.6-73.4%), diabetes (26.5-30.8%), and chronic kidney disease (8.62-22.5%) increased, as did the Charlson comorbidity index (CCI ≥ 3 from 20.0% to 25.1%) (all P < 0.001). Total mortality decreased at 30 days (1.43-1.09%) and 1 year (9.51-8.13%) after implantation (both P < 0.001). At 2 years, total mortality [hazard ratio (HR): 0.72; 95% confidence interval (CI) 0.69-0.76] and total mortality or HF hospitalization (HR: 0.59; 95% CI 0.57-0.62) decreased from 2010-2011 to 2018-2019, after correction for age, race, sex, device type (CRT-defibrillation or pacing), comorbidities (hypertension, diabetes, chronic kidney disease, and myocardial infarction), or the CCI (HR: 0.81; 95% CI 0.77-0.85). CONCLUSIONS: From the perspective of an entire public health system, survival has improved and HF hospitalizations have decreased after CRT implantation over the past decade. This prognostic improvement has occurred despite an increasing comorbidity burden.

Laser Doppler flow for the hemodynamic differentiation of tachycardia.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) offer effective therapy for the prevention of sudden cardiac death (SCD) due to ventricular arrhythmias. However, inappropriate shocks have detrimental effects on survival and quality of life. The addition of hemodynamic monitoring may be useful in discriminating clinically important ventricular arrhythmias. OBJECTIVE: In this study, we assess the ability of laser Doppler flowmetry to assess the hemodynamic effect of paced atrial and ventricular arrhythmias using mean arterial blood pressure as the reference. METHODS: In this acute human study in patients undergoing an elective electrophysiological study, laser Doppler flowmetry, arterial blood pressure, and surface ECG were acquired during high-rate atrial and ventricular pacing to simulate supraventricular and ventricular tachycardias. RESULTS: Arterial blood pressure and laser Doppler flow signals correlated well during atrial and ventricular pacing (rho = 0.694, p < .001). The hemodynamic impairment detected by both methods was greater during ventricular pacing than atrial pacing (-1.0% vs. 19.0%, p < .001). Laser Doppler flowmetry performed better than rate alone to identify hemodynamic impairments. CONCLUSION: In this acute study, laser Doppler flowmetry tissue perfusion served as a good surrogate measure for arterial pressure, which could be incorporated into future ICDs.

Greyzone myocardial fibrosis and ventricular arrhythmias in patients with a left ventricular ejection fraction >35.

AIMS: To determine whether myocardial fibrosis and greyzone fibrosis (GZF) on cardiovascular magnetic resonance (CMR) is associated with ventricular arrhythmias in patients with coronary artery disease (CAD) and a left ventricular ejection fraction (LVEF) >35%. METHODS AND RESULTS: In this retrospective study of CAD patients, GZF mass using the 3SD method (GZF3SD) and total fibrosis mass using the 2SD method (TF2SD) on CMR were assessed in relation to the primary, combined endpoint of sudden cardiac death, ventricular tachycardia, ventricular fibrillation, or resuscitated cardiac arrest. Among 701 patients [age: 65.8 ± 12.3 years (mean ± SD)], 28 (3.99%) patients met the primary endpoint over 5.91 years (median; interquartile range 4.42-7.64). In competing risks analysis, a GZF3SD mass ≥5.0 g was strongly associated with the primary endpoint [subdistribution hazard ratio (sHR): 17.4 (95% confidence interval, CI 6.64-45.5); area under receiver operator characteristic curve (AUC): 0.85, P < 0.001]. A weaker association was observed for TF2SD mass ≥23 g [sHR 10.4 (95% CI 4.22-25.8); AUC: 0.80, P < 0.001]. The range of sHRs for GZF3SD mass (1-527) was wider than for TF2SD mass (1-37.6). CONCLUSIONS: In CAD patients with an LVEF >35%, GZF3SD mass was strongly associated with the arrhythmic endpoint. These findings hold promise for its use in identifying patients with CAD and an LVEF >35% at risk of arrhythmic events.

Right ventricular function and long-term clinical outcomes after cardiac resynchronization therapy: A cardiovascular magnetic resonance study.

BACKGROUND: Right ventricular (RV) dysfunction has been linked to a poor response to cardiac resynchronization therapy (CRT). We sought to determine whether cardiovascular magnetic resonance (CMR)-derived measures of RV function influence clinical outcomes after CRT. METHODS: In this retrospective study, we used CMR to assess pre-implant RV volumes and RV ejection fraction (RVEF) in relation to clinical outcomes after CRT implantation. RESULTS: Among 243 patients (age: 70.3 ± 10.8 years [mean ± SD]; 68.7% male; 121 [49.8%]) with ischemic cardiomyopathy and 122 (50.2%) with nonischemic cardiomyopathy, 141 (58%) after CRT-defibrillation (CRT-D) and 102 (42%) after CRT-pacing (CRT-P), 101 (41.6.0%) patients died, 61 (25.1%) from cardiac causes and 24 (9.88%) from noncardiac causes, over 5.87 years (median; interquartile range: 4.35-7.73). Two (0.82%) patients underwent cardiac transplantation and four (1.64%) had a left ventricular assist device (LVAD). A total of 41 (16.9%) met the composite endpoint of sudden cardiac death (SCD), ventricular tachycardia, or ventricular fibrillation. In univariate analyses, no measure of RV function was associated with total mortality or the arrhythmic endpoint. RVEF was associated with cardiac mortality on univariate analyses (HR per 10%: 0.82, 95% CI 0.70-0.96), but not on multivariate analyses that included left ventricular ejection fraction. CONCLUSIONS: There is no relationship between measures of RV function, such as RV volumes and RVEF, and the long-term clinical outcome of CRT. These findings indicate that such measures should not be considered in patient selection.

Cardiac operations and interventions during the COVID-19 pandemic: a nationwide perspective.

AIMS: The COVID-19 pandemic has led to a decline in hospitalizations for non-COVID-19-related conditions. We explored the impact of the COVID-19 pandemic on cardiac operations and interventions undertaken in England. METHODS AND RESULTS: An administrative database covering hospital activity for England, the Health Episodes Statistics, was used to assess a total of 286 697 hospitalizations for cardiac operations and interventions, as well as 227 257 hospitalizations for myocardial infarction (MI) and 453 799 for heart failure (HF) from 7 January 2019 to 26 July 2020. Over the 3 months of 'lockdown', total numbers and mean reductions in weekly rates [n (-%)], compared with the same time period in 2019, were: coronary artery bypass grafting [-2507 (-64%)]; percutaneous coronary intervention [-5245 (-28%)]; surgical [-1324 (-41%)] and transcatheter [-284 (-21%)] aortic valve replacement; mitral valve replacement; implantation of pacemakers [-6450 (-44%)], cardiac resynchronization therapy with [-356 (-42%)] or without [-491 (-46%)] defibrillation devices, and implantable cardioverter-defibrillators [-501 (-45%)]; atrial fibrillation ablation [-1902 (-83%)], and other ablations [-1712 (-64%)] (all P < 0.001). Over this period, there were 21 038 fewer procedures than in the reference period in 2019 (P < 0.001). These changes paralleled reductions in hospitalizations for MI [-10 794 (-27%)] and HF [-63 058 (-28%)] (both P < 0.001). CONCLUSIONS: The COVID-19 pandemic has led to substantial reductions in the number of cardiac operations and interventions undertaken. An alternative strategy for healthcare delivery to patients with cardiac conditions during the COVID-19 pandemic is urgently needed.

Prognosis of incidental left bundle branch block.

AIMS: Incidental left bundle branch block (iLBBB) is a frequent cause for cardiology referrals. In such instances, there is uncertainty as to its prognosis. We sought to determine the utility of cardiovascular magnetic resonance (CMR) in the risk stratification of patients with iLBBB. METHODS AND RESULTS: Clinical events were collected in patients with iLBBB who had CMR. Controls had no cardiac symptoms or cardiac disease, a normal CMR scan and electrocardiogram. Amongst patients with iLBBB [n = 193, aged 62.7 ± 12.6 years (mean ± SD)], 110/193 (56.9%) had an abnormal phenotype (iLBBBCMR+) and 83/110 (43.0%) had a normal phenotype (iLBBBCMR-). Over 3.75 years (median; inter-quartile range: 2.7-5.5), iLBBBCMR+ had a higher total mortality [adjusted hazard ratio (aHR) 6.49, 95% confidence interval (CI) 1.91-22.0] and total mortality or major adverse cardiac events (MACEs; aHR 9.15, 95% CI 2.56-32.6) than controls (n = 107). In contrast, iLBBBCMR- had a similar risk of total mortality compared with controls, but total mortality or MACEs was higher (aHR 4.24, 95% CI 1.17-15.4; P = 0.028). Amongst iLBBB patients, both myocardial fibrosis (aHR 5.15, 95% CI 1.53-17.4) and left ventricular ejection fraction (LVEF) ≤ 50% (aHR 3.88, 95% CI 1.67-9.06) predicted total mortality. Myocardial fibrosis plus LVEF ≤50% was associated with the highest risk of total mortality (aHR: 9.87, 95% CI 2.99-32.6) and total mortality or MACEs (aHR 3.98, 95% CI 1.73-9.11). CONCLUSIONS: Outcomes in iLBBBCMR+ were poor whereas survival in iLBBBCMR- was comparable with controls. Myocardial fibrosis and LVEF <50% had an additive effect on the risk of clinical outcomes. A CMR scan is pivotal in risk-stratifying patients with iLBBB.

Survival after cardiac resynchronization therapy: results from 50 084 implantations.

AIMS: Randomized controlled trials have shown that cardiac resynchronization therapy (CRT) prolongs survival in patients with heart failure. No studies have explored survival after CRT in relation to individuals in the general population (relative survival, RS). We sought to determine observed and RS after CRT in a nationwide cohort undergoing CRT. METHODS AND RESULTS: A national administrative database was used to quantify observed mortality for patients undergoing CRT. Relative survival (RS) was quantified using life tables. In 50 084 patients [age 72.1 ± 11.6 years (mean ± standard deviation)] undergoing CRT with (CRT-D) (n = 25 273) or without (CRT-P) defibrillation (n = 24 811) over 8.8 years (median follow-up 2.7 years, interquartile range 1.3-4.8), expected survival decreased with age. Device type, male sex, ischaemic heart disease, diabetes, and chronic kidney disease predicted excess mortality. In multivariate analyses, excess mortality (analogue of RS) was lower after CRT-D than after CRT-P in all patients [adjusted hazard ratio (aHR) 0.80, 95% confidence interval (CI) 0.76-0.84] as well as in subgroups with (aHR 0.79, 95% CI 0.74-0.84) or without (aHR 0.82, 95% CI 0.74-0.91) ischaemic heart disease. A Charlson Comorbidity Index (CCI) ≥3 portended a higher excess mortality (aHR 3.04, 95% CI 2.76-3.34). Relative survival was higher in 2015-2017 than in 2009-2011 (aHR 0.64, 95% CI 0.59-0.69). CONCLUSION: Reference RS data after CRT is presented. Sex, ischaemic heart disease, diabetes, chronic kidney disease, and CCI were major determinants of RS after CRT. CRT-D was associated with a higher RS than CRT-P in patients with or without ischaemic heart disease. Relative survival after CRT improved from 2009 to 2017.

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry.

AIMS: To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]. CONCLUSION: Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.

Long-term outcomes of cardiac resynchronization therapy in adult congenital heart disease.

BACKGROUND AND AIMS: Randomized, controlled trials of cardiac resynchronization therapy (CRT) excluded patients with adult congenital heart disease (ACHD). We sought to explore long-term clinical outcomes. METHODS AND RESULTS: In this single-center, observational study, events were collected from hospital records on patients with structural ACHD (sACHD) and adults with ischemic (ICM) or nonischemic (NICM) cardiomyopathy undergoing CRT. Patients with sACHD (n = 23, age: 41.6 ± 13.5 years [mean ± standard deviation]) and adults with ICM (n = 533) or NICM (n = 458) were followed-up for 4.1 years (median; interquartile range: 2.2-6.1). Total mortality was 5/23 (21.7%; 4.4 per 100 person-years) in sACHD, 221/533 (41.5%; 11.8 per 100 person-years) in ICM, and 154/458 (33.6%; 9.7 per 100 person-years) in NICM. In univariate analyses, total mortality in sACHD was lower than in ICM (hazard ratio [HR]: 0.38; 95% confidence interval [CI] 0.15-0.91), but similar to NICM (HR: 0.48, 95% CI 0.20-1.16). Cardiac mortality in sACHD was similar to ICM (HR: 0.78, 95% CI 0.32-1.92) and NICM (HR: 1.12, 95% CI 0.45-2.78). Heart failure (HF) hospitalization rates were similar to ICM (HR: 0.44, 95% CI 0.11-1.77) and NICM (HR: 0.75, 95% CI 0.18-3.08). In multivariate analyses, no differences emerged in total mortality, cardiac mortality, or HF hospitalization between sACHD and NICM or ICM, after adjustment for age, sex, New York Heart Association class, diabetes, atrial rhythm, QRS duration, QRS morphology, systemic ventricular ejection fraction, and medical therapy. CONCLUSION: Total mortality, cardiac mortality, and HF hospitalization after CRT in patients with sACHD was similar to adults with ICM or NICM.

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.

Long-term clinical outcomes of cardiac resynchronization therapy with or without defibrillation: impact of the aetiology of cardiomyopathy.

Aims: There is a continuing debate as to whether cardiac resynchronization therapy-defibrillation (CRT-D) is superior to CRT-pacing (CRT-P), particularly in patients with non-ischaemic cardiomyopathy (NICM). We sought to quantify the clinical outcomes after primary prevention of CRT-D and CRT-P and identify whether these differed according to the aetiology of cardiomyopathy. Methods and results: Analyses were undertaken in the total study population of patients treated with CRT-D (n = 551) or CRT-P (n = 999) and in propensity-matched samples. Device choice was governed by the clinical guidelines in the United Kingdom. In univariable analyses of the total study population, for a maximum follow-up of 16 years (median 4.7 years, interquartile range 2.4-7.1), CRT-D was associated with a lower total mortality [hazard ratio (HR) 0.72] and the composite endpoints of total mortality or heart failure (HF) hospitalization (HR 0.72) and total mortality or hospitalization for major adverse cardiac events (MACE; HR 0.71) (all P < 0.001). After propensity matching (n = 796), CRT-D was associated with a lower total mortality (HR 0.72) and the composite endpoints (all P < 0.01). When further stratified according to aetiology, CRT-D was associated with a lower total mortality (HR 0.62), total mortality or HF hospitalization (HR 0.63), and total mortality or hospitalization for MACE (HR 0.59) (all P < 0.001) in patients with ischaemic cardiomyopathy (ICM). There were no differences in outcomes between CRT-D and CRT-P in patients with NICM. Conclusion: In this study of real-world clinical practice, CRT-D was superior to CRT-P with respect to total mortality and composite endpoints, independent of known confounders. The benefit of CRT-D was evident in ICM but not in NICM.

Clinical outcomes after upgrading from pacemakers to cardiac resynchronization therapy.

BACKGROUND AND AIMS: Right ventricular pacing may lead to heart failure (HF). Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded from most randomized, controlled trials. We sought to determine the long-term outcomes of upgrading from pacemakers to CRT with (CRT-D) or without (CRT-P) defibrillation in patients with no history of sustained ventricular arrhythmias. METHODS AND RESULTS: In this observational study, clinical events were quantified in relation to the type of implant (de novo or upgrade) and device type at upgrade (CRT-P or CRT-D). Patients underwent CRT implantation (n = 1,545; 1,314 [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years [interquartile range: 2.4-7.0]. In analyses of crude event rates, upgrades had a higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI] 0.10-1.61), a higher total mortality or HF hospitalization (aHR: 1.26; 95% CI 1.05-1.51), but similar mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96-1.38). No group differences emerged in any of these endpoints after propensity score matching. After inverse probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36-0.73), total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34-0.79), and total mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40-0.82) were lower after CRT-D than after CRT-P. CONCLUSION: Upgrading from pacemakers to CRT was associated with a similar long-term risk of mortality and morbidity to de novo CRT. After upgrade, CRT-D was associated with a lower mortality than CRT-P.

Arrhythmic Risk Stratification by Cardiovascular Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs). OBJECTIVES: This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM). METHODS: Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia). RESULTS: The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MFVA) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and ≤10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MFVA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01). CONCLUSIONS: MFVA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MFVA. In contrast, LVEF was a poor discriminator of arrhythmic risk.

Diagnostic yield of a heart failure referral pathway using N-terminal pro-brain natriuretic peptide.

OBJECTIVE: To determine the diagnostic yield of a 'high' N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with suspected heart failure (HF) referred from primary to secondary care. METHODS: In this retrospective study, cardiac diagnoses were quantified in consecutive patients with an NT-proBNP>400 ng/L referred from primary care centres to a specialist HF service. RESULTS: Among 654 consecutive patients (age: 78.5±9.72 years; 45.9% men; left ventricular ejection fraction (LVEF): 55.4±12.5% (mean±SD)), the primary diagnoses were: valvular disease (39.4%), HF (29.2%; 13.3% with LVEF<40%) and atrial fibrillation (AF; 17.3%). In terms of primary or secondary diagnoses, 68% of patients had valve disease, 46.9% had AF and 29.2% had HF. A cardiac diagnosis was made in 85.9%. In multivariable analyses, NT-proBNP predicted HF with LVEF<40% (OR: 10.2, 95% CI: 5.63 to 18.3) and HF with any LVEF (OR: 6.13, 95% CI: 3.79 to 9.93). In canonical linear discriminant analyses, NT-proBNP correctly identified 54.5% of patients with HF. The remainder were misclassified as valvular disease, AF or no cardiac diagnosis. CONCLUSION: Among patients with an NT-proBNP>400 ng/L referred through a primary care HF pathway, most patients had valve disease or AF rather than HF. NT-proBNP cannot discriminate among HF, valve disease and AF. On this basis, NT-proBNP may be best employed in detecting cardiac disease in general rather than HF per se.

Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation.

BACKGROUND: Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias. OBJECTIVES: The purpose of this study was to determine whether presence of myocardial fibrosis on visual assessment (MFVA) and gray zone fibrosis (GZF) mass predicts sudden cardiac death (SCD) and ventricular fibrillation/sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation. METHODS: In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of SCD and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation. RESULTS: Among 700 patients (age 68.0 ± 12.0 years), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over median 6.93 years (IQR: 5.82-9.32 years). MFVA predicted SCD (HR: 26.3; 95% CI: 3.7-3,337; negative predictive value: 100%). In competing risk analyses, MFVA also predicted the arrhythmic endpoint (subdistribution HR: 19.9; 95% CI: 6.4-61.9; negative predictive value: 98.6%). Compared with no MFVA, a GZF mass measured with the 5SD method (GZF5SD) >17 g was associated with highest risk of SCD (HR: 44.6; 95% CI: 6.12-5,685) and the arrhythmic endpoint (subdistribution HR: 30.3; 95% CI: 9.6-95.8). Adding GZF5SD mass to MFVA led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint. CONCLUSIONS: In CIED recipients, MFVA excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF5SD mass added predictive value in relation to SCD and the arrhythmic endpoint.

Cardiac device implantation and device usage in Fabry and hypertrophic cardiomyopathy.

BACKGROUND: Fabry disease (FD) is a treatable X-linked condition leading to progressive cardiac disease, arrhythmia and premature death. We aimed to increase awareness of the arrhythmogenicity of Fabry cardiomyopathy, by comparing device usage in patients with Fabry cardiomyopathy and sarcomeric HCM. All Fabry patients with an implantable cardioverter defibrillator (ICD) implanted in the UK over a 17 year period were included. A comparator group of HCM patients, with primary prevention ICD implantation, were captured from a regional registry database. RESULTS: Indications for ICD in FD varied with 72% implanted for primary prevention based on multiple potential risk factors. In FD and HCM primary prevention devices, arrhythmia occurred more frequently in FD over shorter follow-up (HR 4.2, p < 0.001). VT requiring therapy was more common in FD (HR 4.5, p = 0.002). Immediate shock therapy for sustained VT was also more common (HR 2.5, p < 0.001). There was a greater burden of AF needing anticoagulation and NSVT in FD (AF: HR 6.2, p = 0.004, NSVT: HR 3.1, p < 0.001). CONCLUSION: This study demonstrates arrhythmia burden and ICD usage in FD is high, suggesting that Fabry cardiomyopathy may be more 'arrhythmogenic' than previously thought. Existing risk models cannot be mutually applicable and further research is needed to provide clarity in managing Fabry patients with cardiac involvement.

Myocardial Fibrosis as a Predictor of Sudden Death in Patients With Coronary Artery Disease.

BACKGROUND: The "gray zone" of myocardial fibrosis (GZF) on cardiovascular magnetic resonance may be a substrate for ventricular arrhythmias (VAs). OBJECTIVES: The purpose of this study was to determine whether GZF predicts sudden cardiac death (SCD) and VAs (ventricular fibrillation or sustained ventricular tachycardia) in patients with coronary artery disease (CAD) and a wide range of left ventricular ejection fractions (LVEFs). METHODS: In this retrospective study of CAD patients, the presence of myocardial fibrosis on visual assessment (MFVA) and GZF mass in patients with MFVA were assessed in relation to SCD and the composite, arrhythmic endpoint of SCD or VAs. RESULTS: Among 979 patients (mean age [± SD]: 65.8 ± 12.3 years), 29 (2.96%) experienced SCD and 80 (8.17%) met the arrhythmic endpoint over median 5.82 years (interquartile range: 4.1 to 7.3 years). In the whole cohort, MFVA was strongly associated with SCD (hazard ratio: 10.1; 95% confidence interval [CI]: 1.42 to 1,278.9) and the arrhythmic endpoint (hazard ratio: 28.0; 95% CI: 4.07 to 3,525.4). In competing risks analyses, associations between LVEF <35% and SCD (subdistribution hazard ratio [sHR]: 2.99; 95% CI: 1.42 to 6.31) and the arrhythmic endpoint (sHR: 4.71; 95% CI: 2.97 to 7.47) were weaker. In competing risk analyses of the MFVA subcohort (n = 832), GZF using the 3SD method (GZF3SD) >5.0 g was strongly associated with SCD (sHR: 10.8; 95% CI: 3.74 to 30.9) and the arrhythmic endpoint (sHR: 7.40; 95% CI: 4.29 to 12.8). Associations between LVEF <35% and SCD (sHR: 2.62; 95% CI: 1.24 to 5.52) and the arrhythmic endpoint (sHR: 4.14; 95% CI: 2.61 to 6.57) were weaker. CONCLUSIONS: In CAD patients, MFVA plus quantified GZF3SD mass was more strongly associated with SCD and VAs than LVEF. In selecting patients for implantable cardioverter-defibrillators, assessment of MFVA followed by quantification of GZF3SD mass may be preferable to LVEF.

Effect of QRS area reduction and myocardial scar on the hemodynamic response to cardiac resynchronization therapy.

BACKGROUND: Vectorcardiographic QRS area (QRSarea) predicts clinical outcomes after cardiac resynchronization therapy (CRT). Myocardial scar adversely affects clinical outcomes after CRT. OBJECTIVE: The purpose of this study in patients with an ideally deployed quadripolar left ventricular (LV) lead (QUAD) was to determine whether reducing QRSarea leads to an acute hemodynamic response (AHR) and whether scar affects this interaction. METHODS: Patients (n = 26; age 69.2 ± 9.12 years [mean ± SD]) underwent assessment of the maximum rate of change of LV pressure (ΔLV dP/dtmax) during CRT using various left ventricular pacing locations (LVPLs). Cardiac magnetic resonance (CMR) scan was used to localize LV myocardial scar. RESULTS: Interindividually, ΔQRSarea (area under the receiver operating characteristic curve [AUC] 0.81; P <.001) and change in QRS duration (ΔQRSd) (AUC 0.76; P <.001) predicted ΔLV dP/dtmax after CRT. Scar burden correlated with ΔQRSarea (r = 0.35; P = .003), ΔQRSarea (r = 0.35; P = .003), and ΔQRSd (r = 0.46; P <.001). A reduction in QRSarea was observed with LVPLs remote from scar (-3.28 ± 38.1 µVs) or in LVPLs in patients with no scar at all (-43.8 ± 36.8 µVs), whereas LVPLs over scar increased QRSarea (22.2 ± 58.4 µVs) (P <.001 for all comparisons). LVPLs within 1 scarred LV segment were associated with lower ΔLV dP/dtmax (-2.21% ± 11.5%) than LVPLs remote from scar (5.23% ± 10.3%; P <.001) or LVPLs in patients with no scar at all (10.2% ± 7.75%) (both P <.001). CONCLUSION: Reducing QRSarea improves the AHR to CRT. Myocardial scar adversely affects ΔQRSarea and the AHR. These findings may support the use of ΔQRSarea and CMR in optimizing CRT using QUAD.

Sex-Specific Differences in Survival and Heart Failure Hospitalization After Cardiac Resynchronization Therapy With or Without Defibrillation.

Background Women are underrepresented in cardiac resynchronization therapy (CRT) trials. Some studies suggest that women fare better than men after CRT. We sought to explore clinical outcomes in women and men undergoing CRT-defibrillation or CRT-pacing in real-world clinical practice. Methods and Results A national database (Hospital Episode Statistics for England) was used to quantify clinical outcomes in 43 730 patients (women: 10 890 [24.9%]; men: 32 840 [75.1%]) undergoing CRT over 7.6 years, (median follow-up 2.2 years, interquartile range, 1-4 years). In analysis of the total population, the primary end point of total mortality (adjusted hazard ratio [aHR], 0.73; 95% CI, 0.69-0.76) and the secondary end point of total mortality or heart failure hospitalization (aHR, 0.79, 95% CI 0.75-0.82) were lower in women, independent of known confounders. Total mortality (aHR, 0.73; 95% CI, 0.70-0.76) and total mortality or heart failure hospitalization (aHR, 0.79; 95% CI, 0.75-0.82) were lower for CRT-defibrillation than for CRT-pacing. In analyses of patients with (aHR, 0.89; 95% CI, 0.80-0.98) or without (aHR, 0.70; 95% CI, 0.66-0.73) a myocardial infarction, women had a lower total mortality. In sex-specific analyses, total mortality was lower after CRT-defibrillation in women (aHR, 0.83; P=0.013) and men (aHR, 0.69; P<0.001). Conclusions Compared with men, women lived longer and were less likely to be hospitalized for heart failure after CRT. In both sexes, CRT-defibrillation was superior to CRT-pacing with respect to survival and heart failure hospitalization. The longest survival after CRT was observed in women without a history of myocardial infarction.