Use of torsades de pointes risk drugs among patients with out-of-hospital cardiac arrest and likelihood of shockable rhythm and return of spontaneous circulation: A nationwide study.

AIM: Treatment with certain drugs can augment the risk of developing malignant arrhythmias (e.g. torsades de pointes [TdP]). Hence, we examined the overall TdP risk drug use before out-of-hospital cardiac arrest (OHCA) and possible association with shockable rhythm and return of spontaneous circulation (ROSC). METHODS: Patients ≥18 years with an OHCA of cardiac origin from the Danish Cardiac Arrest Registry (2001-2014) and TdP risk drug use according to www.CredibleMeds.org were identified. Factors associated with TdP risk drug use and secondly how use may affect shockable rhythm and ROSC were determined by multivariable logistic regression. RESULTS: We identified 27,481 patients with an OHCA of cardiac origin (median age: 72 years [interquartile range 62.0, 80.0 years]). A total of 37% were in treatment with TdP risk drugs 0-30 days before OHCA compared with 33% 61-90 days before OHCA (p < 0.001). Most commonly used TdP risk drugs were citalopram (36.1%) and roxithromycin (10.7%). Patients in TdP risk drug treatment were older (75 vs 70 years) and more comorbid compared with those not in treatment. Subsequently, TdP risk drug use was associated with less likelihood of the presenting rhythm being shockable (odds ratio [OR] = 0.63, 95% confidence interval [CI]:0.58-0.69) and ROSC (OR = 0.73, 95% CI:0.66-0.80). CONCLUSION: TdP risk drug use increased in the time leading up to OHCA and was associated with reduced likelihood of presenting with a shockable rhythm and ROSC in an all-comer OHCA setting. However, patients in TdP risk drug treatment were older and more comorbid than patients not in treatment.

Segment Length in Cine Strain Analysis Predicts Cardiac Resynchronization Therapy Outcome Beyond Current Guidelines.

BACKGROUND: Patients with a class I recommendation for cardiac resynchronization therapy (CRT) are likely to benefit, but the effect of CRT in class II patients is more heterogeneous and additional selection parameters are needed in this group. The recently validated segment length in cine strain analysis of the septum (SLICE-ESSsep) measurement on cardiac magnetic resonance cine imaging predicts left ventricular functional recovery after CRT but its prognostic value is unknown. This study sought to evaluate the prognostic value of SLICE-ESSsep for clinical outcome after CRT. METHODS: Two hundred eighteen patients with a left bundle branch block or intraventricular conduction delay and a class I or class II indication for CRT who underwent preimplantation cardiovascular magnetic resonance examination were enrolled. SLICE-ESSsep was manually measured on standard cardiovascular magnetic resonance cine imaging. The primary combined end point was all-cause mortality, left ventricular assist device, or heart transplantation. Secondary end points were (1) appropriate implantable cardioverter defibrillator therapy and (2) heart failure hospitalization. RESULTS: Two-thirds (65%) of patients had a positive SLICE-ESSsep ≥0.9% (ie, systolic septal stretching). During a median follow-up of 3.8 years, 66 (30%) patients reached the primary end point. Patients with positive SLICE-ESSsep were at lower risk to reach the primary end point (hazard ratio 0.36; P<0.001) and heart failure hospitalization (hazard ratio 0.41; P=0.019), but not for implantable cardioverter defibrillator therapy (hazard ratio, 0.66; P=0.272). Clinical outcome of class II patients with a positive ESSsep was similar to those of class I patients (hazard ratio, 1.38 [95% CI, 0.66-2.88]; P=0.396). CONCLUSIONS: Strain assessment of the septum (SLICE-ESSsep) provides a prognostic measure for clinical outcome after CRT. Detection of a positive SLICE-ESSsep in patients with a class II indication predicts improved CRT outcome similar to those with a class I indication whereas SLICE-ESSsep negative patients have poor prognosis after CRT implantation.

Socioeconomic disparities in prehospital factors and survival after out-of-hospital cardiac arrest.

OBJECTIVE: It remains unknown whether patient socioeconomic factors affect interventions and survival after out-of-hospital cardiac arrest (OHCA), and whether a socioeconomic effect on bystander interventions affects survival. Therefore, this study examined patient socioeconomic disparities in prehospital factors and survival. METHODS: From the Danish Cardiac Arrest Registry, patients with OHCA ≥30 years were identified, 2001-2014, and divided into quartiles of household income (highest, high, low, lowest). Associations between income and bystander cardiopulmonary resuscitation (CPR) and 30-day survival with bystander CPR as mediator were analysed by logistic regression and mediation analysis in private witnessed, public witnessed, private unwitnessed and public unwitnessed arrests, adjusted for confounders. RESULTS: We included 21 480 patients. Highest income patients were younger, had higher education and were less comorbid relative to lowest income patients. They had higher odds for bystander CPR with the biggest difference in private unwitnessed arrests (OR 1.74, 95% CI 1.47 to 2.05). For 30-day survival, the biggest differences were in public witnessed arrests with 26.0% (95% CI 22.4% to 29.7%) higher survival in highest income compared with lowest income patients. Had bystander CPR been the same for lowest income as for highest income patients, then survival would be 25.3% (95% CI 21.5% to 29.0%) higher in highest income compared with lowest income patients, resulting in elimination of 0.79% (95% CI 0.08% to 1.50%) of the income disparity in survival. Similar trends but smaller were observed in low and high-income patients, the other three subgroups and with education instead of income. From 2002 to 2014, increases were observed in both CPR and survival in all income groups. CONCLUSION: Overall, lower socioeconomic status was associated with poorer prehospital factors and survival after OHCA that was not explained by patient or cardiac arrest-related factors.

Concomitant changes in ventricular depolarization and repolarization and long-term outcomes of biventricular pacing.

BACKGROUND: Biventricular (BiV) pacing increases transmural repolarization heterogeneity due to epicardial to endocardial conduction from the left ventricular (LV) lead. However, limited evidence is available on concomitant changes in ventricular depolarization and repolarization and long-term outcomes of BiV pacing. Therefore, we investigated associations of BiV pacing-induced concomitant changes in ventricular depolarization and repolarization with mortality (i.e., LV assist device, heart transplantation, or all-cause mortality) and sustained ventricular arrhythmia endpoints. METHODS: Consecutive BiV-defibrillator recipients with digital preimplantation and postimplantation electrocardiograms recorded between 2006 and 2015 at Duke University Medical Center were included. We calculated changes in QRS duration and corrected JT (JTc) interval and split them by median values. For simplicity, these variables were named QRSdecreased (≤ -12 ms), QRSincreased (> -12 ms), JTcdecreased (≤22 ms), and JTcincreased (> 22 ms) and subsequently used to construct four mutually exclusive groups. RESULTS: We included 528 patients (median age, 68 years; male, 69%). No correlation between changes in QRS duration and JTc interval was observed (P = .295). Compared to QRSdecreased /JTcincreased , increased risk of the composite mortality endpoint was associated with QRSdecreased /JTcdecreased (hazard ratio [HR] = 1.62; 95% confidence interval [CI] = 1.09-2.43), QRSincreased /JTcdecreased (HR = 1.86; 95% CI = 1.27-2.71), and QRSincreased /JTcincreased (HR = 2.25; 95% CI = 1.52-3.35). No QRS/JTc group was associated with excess sustained ventricular arrhythmia risk (P = .400). CONCLUSION: Among BiV-defibrillator recipients, QRSdecreased /JTcincreased was associated with the most favorable long-term survival free of LV assist device, heart transplantation, and sustained ventricular arrhythmias. Our findings suggest that improved electrical resynchronization may be achieved by assessing concomitant changes in ventricular depolarization and repolarization.

Lead one ratio in left bundle branch block predicts poor cardiac resynchronization therapy response.

BACKGROUND: A low electrocardiogram (ECG) lead one ratio (LOR) of the maximum positive/negative QRS amplitudes is associated with lower left ventricular ejection fraction (LVEF) and worse outcomes in left bundle branch block (LBBB); however, the impact of LOR on cardiac resynchronization therapy (CRT) outcomes is unknown. We compared clinical outcomes and echocardiographic changes after CRT implantation by LOR. METHODS: Consecutive CRT-defibrillator recipients with LBBB implanted between 2006 and 2015 at Duke University Medical Center were included (N = 496). Time to heart transplant, left ventricular assist device (LVAD) implantation, or death was compared among patients with LOR <12 vs ≥12 using Cox-proportional hazard models. Changes in LVEF and LV volumes after CRT were compared by LOR. RESULTS: Baseline ECG LOR <12 was associated with an adjusted hazard ratio (HR) of 1.69 (95% CI: 1.12-2.40, P = .01) for heart transplant, LVAD, or death. Patients with LOR <12 had less reduction of LV end diastolic volume (ΔLVEDV -4 ± 21 vs -13 ± 23%, P = .04) and LV end systolic volume (ΔLVESV -9 ± 27 vs -22 ± 26%, P = .03) after CRT. In patients with QRS duration (QRSd) ≥150 ms, LOR <12 was associated with an adjusted HR of 2.01 (95% CI 1.21-3.35, P = .008) for heart transplant, LVAD, or death, compared with LOR ≥12. CONCLUSIONS: Baseline ECG LOR <12 portends worse outcomes after CRT implantation in patients with LBBB, specifically among those with QRSd ≥150 ms. This ECG ratio may identify patients with a class I indication for CRT implantation at high risk for poor postimplantation outcomes.

Electrocardiogram Characteristics and Their Association With Psychotropic Drugs Among Patients With Schizophrenia.

BACKGROUND: There are limited data on electrocardiogram (ECG) characteristics and their association with psychotropic drugs in schizophrenia. METHODS: Using a cross-sectional design, we included Danish primary care patients with first-time digital ECGs from 2001 to 2015. Patients diagnosed with schizophrenia before ECG recording were matched 1:5 on age, sex, and ECG recording year to controls without psychiatric disease. Multivariable logistic regression was used to compute odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We included 4486 patients with schizophrenia matched with 22 430 controls (median age, 47 years; male, 55%). Between groups, the prevalence of abnormal ECGs was similar (54%, P = .536), but patients with schizophrenia demonstrated higher median heart rate (79 vs 69 beats per minute, P < .001) and Fridericia-corrected QT (QTc) interval (416 vs 412 ms, P < .001) than controls. QTc prolongation was also more prevalent among patients with schizophrenia (3.4% vs 1.1%, P < .001), and so were pathological Q waves (5.3% vs 3.9%, P < .001). Patients with schizophrenia less frequently demonstrated left ventricular hypertrophy (6.1% vs 9.6%, P < .001) and atrial fibrillation or flutter (0.7% vs 1.4%, P < .001). Among patients with schizophrenia only, particularly antipsychotics were associated with abnormal ECGs (OR, 1.20; 95% CI, 1.04-1.39). CONCLUSIONS: Patients with schizophrenia demonstrate a different cardiovascular risk profile than matched controls without psychiatric disease, with higher prevalence of elevated heart rate, QTc prolongation, and pathological Q waves, and lower prevalence of left ventricular hypertrophy and atrial fibrillation or flutter. Particularly antipsychotics were associated with abnormal ECGs. This underscores an integrated care approach when ECG abnormalities are detected in this group.

Long-Term Prognostic Value of Less-Stringent Electrocardiographic Q Waves and Fourth Universal Definition of Myocardial Infarction Q Waves.

BACKGROUND: The Fourth Universal Definition of Myocardial Infarction defines electrocardiographic Q waves as duration ≥30 ms and amplitude ≥1 mm or QS complex in 2 contiguous leads. However, current taskforce criteria may be overly restrictive. Therefore, we investigated the association of isolated, lenient, or strict Q waves with long-term outcome. METHODS: From 2001 to 2015, we included Danish primary care patients with digital electrocardiograms (ECGs) that were evaluated for Q waves. If none occurred, patients had no Q waves. If no other contiguous Q wave occurred, patients had isolated Q waves. If another contiguous Q wave occurred meeting only 1 criterion (≥30 ms and <1 mm or <30 ms and ≥1 mm), patients had lenient Q waves. If another contiguous Q wave occurred, patients had strict Q waves. RESULTS: Of 365,206 patients, 87,957 had isolated, lenient, or strict Q waves (24%; median age, 61 years; male, 48%), and 277,249 had no Q waves (76%; median age, 53 years; male, 42%). Mortality risk was increased with isolated (all-cause adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.29-1.37; cardiovascular-cause aHR, 1.78; 95% CI, 1.70-1.87), lenient (all-cause aHR, 1.41; 95% CI, 1.33-1.50; cardiovascular-cause aHR, 1.78; 95% CI, 1.63-1.94), or strict (all-cause aHR, 1.64; 95% CI, 1.57-1.72; cardiovascular-cause aHR, 2.70; 95% CI, 2.52-2.89) Q waves compared with no Q waves. Highest mortality risk was associated with lenient or strict Q waves in anteroseptal leads. CONCLUSIONS: This large contemporary analysis suggests that less-stringent Q-wave criteria carry prognostic value in predicting adverse outcome among primary care patients.

PR Prolongation predicts inadequate resynchronization with biventricular pacing in left bundle branch block.

BACKGROUND: PR interval prolongation is associated with poor outcome after cardiac resynchronization therapy (CRT) among patients with left bundle branch block (LBBB) but the mechanisms are unknown. We investigated clinical outcomes, electrocardiogram (ECG), and echocardiogram changes after CRT by PR interval. METHODS: This is a retrospective study of CRT recipients with a baseline ejection fraction ≤35% and ECG showing sinus rhythm and LBBB. Patients were stratified by baseline PR interval quartile and the primary combined endpoint was time to heart transplantation, left ventricular assist device (LVAD) implantation, or death. ECG, echocardiogram, and clinical variables were compared to identify mechanisms for observed differences in outcomes. RESULTS: Of 291 eligible patients, the mean age was 65 years, 60% were male, and 19% had prior atrial fibrillation. Patients with PR prolongation (quartile 4, PR > 200 ms) more frequently had a history of atrial fibrillation, coronary artery bypass graft surgery, prior implantable cardioverter defibrillator implantation, and use of amiodarone than patients in PR quartiles 1-3. A PR > 200ms was associated with an adjusted hazard ratio of 1.7 (95% CI: 1.1-2.5) for the primary endpoint. Patients with PR > 200 ms had less reduction in QRS duration and QRS area after CRT while having more increase in QT and QTc intervals than patients with PR ≤ 200 ms. No major differences were observed in echocardiography by baseline PR interval quartiles. CONCLUSIONS: PR prolongation predicts shorter survival free of heart transplantation or LVAD implantation in patients with LBBB. This may be due to inadequate ventricular resynchronization.

Out-of-hospital cardiac arrest in patients with psychiatric disorders - Characteristics and outcomes.

AIMS: To investigate whether the recent improvements in pre-hospital cardiac arrest-management and survival following out-of-hospital cardiac arrest (OHCA) also apply to OHCA patients with psychiatric disorders. METHODS: We identified all adult Danish patients with OHCA of presumed cardiac cause, 2001-2015. Psychiatric disorders were defined by hospital diagnoses up to 10 years before OHCA and analyzed as one group as well as divided into five subgroups (schizophrenia-spectrum disorders, bipolar disorder, depression, substance-induced mental disorders, other psychiatric disorders). Association between psychiatric disorders and pre-hospital OHCA-characteristics and 30-day survival were assessed by multiple logistic regression. RESULTS: Of 27,523 OHCA-patients, 4772 (17.3%) had a psychiatric diagnosis. Patients with psychiatric disorders had lower odds of 30-day survival (0.37 95% confidence interval 0.32-0.43) compared with other OHCA-patients. Likewise, they had lower odds of witnessed status (0.75 CI 0.70-0.80), bystander cardiopulmonary resuscitation (CPR) (0.77 CI 0.72-0.83), shockable heart rhythm (0.37 95% CI, 0.33-0.40), and return of spontaneous circulation (ROSC) at hospital arrival (0.66 CI 0.59-0.72). Similar results were seen in all five psychiatric subgroups. The difference in 30-day survival between patients with and without psychiatric disorders increased in recent years: from 8.4% (CI 7.0-10.0%) in 2006 to 13.9% (CI 12.4-15.4%) in 2015 and from 7.0% (4.3-10.8%) in 2006 to 7.0% (CI 4.5-9.7%) in 2015, respectively. CONCLUSION: Patients with psychiatric disorders have lower survival following OHCA compared to non-psychiatric patients and the gap between the two groups has widened over time.

Thyroid dysfunction and electrocardiographic changes in subjects without arrhythmias: a cross-sectional study of primary healthcare subjects from Copenhagen.

OBJECTIVE: The objective of the present study was to investigate associations of both overt and subclinical thyroid dysfunction with common ECG parameters in a large primary healthcare population. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: The study population comprised of primary healthcare patients in Copenhagen, Denmark, who had a thyroid function test and an ECG recorded within 7 days of each other between 2001 and 2011. DATA SOURCES: The Danish National Patient Registry was used to collect information regarding baseline characteristics and important comorbidities. OUTCOME MEASURE AND STUDY GROUPS: Common ECG parameters were determined using Marquette 12SL software and were compared between the study groups. The study population was divided into five groups based on their thyroid status. Euthyroid subjects served as the reference group in all analyses. RESULTS: A total of 132 707 patients (age 52±17 years; 50% female) were included. Hyperthyroidism was significantly associated with higher heart rate and prolonged QTc interval with significant interaction with age (p<0.009) and sex (p<0.001). These associations were less pronounced for patients with higher age. Subclinical hyperthyroidism was associated with higher heart rate among females, and a similar trend was observed among males. Hypothyroidism was associated with slower heart rate and shorter QTc but only in women. Moreover, longer P-wave duration, longer PR interval and low voltage were observed in patients with both subclinical and overt hypothyroidism. However, the presence of low voltage was less pronounced with higher age (p=0.001). CONCLUSION: Both overt and subclinical thyroid disorders were associated with significant changes in important ECG parameters. Age and gender have significant impact on the association of thyroid dysfunction particularly on heart rate and QTc interval.

The Association of a classical left bundle Branch Block Contraction Pattern by vendor-independent strain echocardiography and outcome after cardiac resynchronization therapy.

BACKGROUND: The association of a Classical left bundle branch block (LBBB) contraction pattern and better outcome after cardiac resynchronization therapy (CRT) has only been studied using vendor-specific software for echocardiographic speckle-tracked longitudinal strain analysis. The purpose of this study was to assess whether a Classical LBBB contraction pattern on longitudinal strain analysis using vendor-independent software is associated with clinical outcome in CRT recipients with LBBB. METHODS: This was a retrospective cohort study including CRT recipients with LBBB, heart failure, and left ventricular (LV) ejection fraction ≤35%. Speckle-tracked echocardiographic longitudinal strain analysis was performed retrospectively on echocardiograms using vendor-independent software. The presence of a Classical LBBB contraction pattern was determined by consensus of two readers. The primary end point was a composite of time to death, heart transplantation or LV assist device implantation. Secondary outcome was ≥15% reduction in LV end-systolic volume. Intra- and inter-reader agreement of the longitudinal strain contraction pattern was assessed by calculating Cohen's κ. RESULTS: Of 283 included patients, 113 (40%) were women, mean age was 66 ± 11 years, and 136 (48%) had ischemic heart disease. A Classical LBBB contraction pattern was present in 196 (69%). The unadjusted hazard ratio for reaching the primary end point was 1.93 (95% confidence interval, 1.36-2.76, p < 0.001) when comparing patients without to patients with a Classical LBBB contraction pattern. Adjusted for ischemic heart disease and QRS duration < 150 milliseconds the hazard ratio was 1.65 (95% confidence interval, 1.12-2.43, p = 0.01). Of the 123 (43%) patients with a follow-up echocardiogram, 64 of 85 (75%) of patients with a Classical LBBB contraction pattern compared to 13 of 38 (34%) without, had ≥15% reduction in LV end-systolic volume (p < 0.001). Cohen's κ were 0.86 (95% confidence interval, 0.71-1.00) and 0.42 (95% confidence interval, 0.30-0.54) for intra- and inter-reader agreement, respectively. CONCLUSION: Using vendor-independent strain software, a Classical LBBB contraction pattern is associated with better outcome in CRT recipients with LBBB, but inter-reader agreement for the classification of contraction pattern is only moderate.

The effect of early-life and adult socioeconomic position on development of lifestyle-related diseases.

BACKGROUND: Early-life socioeconomic position (SEP) is associated with lifestyle-related diseases in adulthood. However, evidence is lacking on the extent to which adult SEP mediates this association. METHODS: Time to either chronic obstructive pulmonary disease (COPD), cardiovascular disease or diabetes were assessed in the Danish population born between 1961 and 1971 (n = 793 674) from age 30 until 2015. Early-life position was assessed in 1981 (by parental) and again at age 30 (own) by four markers; income, occupation, education-divided into high, middle, low-and a combined score for all markers. Using a counterfactual approach, we estimated the total effect of early-life position on disease onset and the degree to which adult position mediated this effect. RESULTS: Results of the time-to-event analysis showed a gradient of all early-life markers on the risk of developing all lifestyle-related diseases. Notably, comparing those in the lowest to the highest educational position, the hazard of COPD was 130% higher for women [hazard ratio = 2.30(95% confidence interval = 2.20-2.41)] and 114% higher for men [2.14 (2.05-2.25)]. About 67%(63-70%) of the effect of educational position was mediated through adult position for COPD, 55% for cardiovascular disease and 50% for diabetes. For the combined score 44, 29 and 33%, respectively, was mediated. CONCLUSION: About one-tenth to two-thirds of the effect of early-life position is mediated by the position attained in adulthood. The degree mediated depend on the outcome investigated, gender and the social position marker used indicating that alternative pathways may play a key role in developing effective policies targeting early-life behaviours.

Association Between Driving Distance From Nearest Fire Station and Survival of Out-of-Hospital Cardiac Arrest.

Background Firefighter first responders dispatched in parallel with emergency medical services ( EMS ) personnel for out-of-hospital cardiac arrests ( OHCA ) can provide early defibrillation to improve survival. We examined whether survival following first responder defibrillation differed according to driving distance from nearest fire station to OHCA site. Methods and Results From the CARES (Cardiac Arrest Registry to Enhance Survival) registry, we identified non- EMS witnessed OHCA s of presumed cardiac cause from 2010 to 2014 in Durham, Mecklenburg, and Wake counties, North Carolina. We used logistic regression to estimate the association between calculated driving distances (≤1, 1-1.5, 1.5-2, and >2 miles) and survival to hospital discharge following first responder defibrillation compared with defibrillation by EMS personnel. In total, 5020 OHCA s were included in the study. First responders more often applied the first automated external defibrillators at the shortest distances (≤1 mile) versus longest distances (>2 miles) (53.4% versus 46.6%, respectively, P<0.001). When compared with EMS defibrillation, first responder defibrillation within 1 mile and 1 to 1.5 miles of the nearest fire station was associated with increased survival to hospital discharge (odds ratio 2.01 [95% confidence interval 1.46-2.78] and odds ratio 1.61 [95% confidence interval 1.10-2.35], respectively). However, at the longest distances (1.5-2.0 and >2.0 miles), survival following first responder defibrillation did not differ from EMS defibrillation (odds ratio 0.77 [95% confidence interval 0.48-1.21] and odds ratio 0.97 [95% confidence interval 0.67-1.41], respectively). Conclusions Shorter driving distance from nearest fire station to OHCA location was associated with improved survival following defibrillation by first responders. These results suggest that the location of first responder units should be considered when organizing prehospital systems of OHCA care.

Size Matters: Normalization of QRS Duration to Left Ventricular Dimension Improves Prediction of Long-Term Cardiac Resynchronization Therapy Outcome.

BACKGROUND: In patients with left bundle branch block (LBBB), QRS duration (QRSd) depends on left ventricular (LV) dimension. Previously, we demonstrated that normalizing QRSd to LV dimension, to adjust for variations in LV size, improved prediction of hemodynamic response to cardiac resynchronization therapy (CRT). In addition, sex-specific differences in CRT outcome have been attributed to normalized QRSd. The present study evaluates the effect of normalization of QRSd to LV dimension on prediction of survival after CRT implantation. METHODS: In this 2-center study, we studied 250 heart failure patients with LV ejection fraction ≤35% and QRSd ≥120 ms who underwent cardiac magnetic resonance imaging before CRT implantation. LV end-diastolic volumes were used for QRSd normalization (ie, QRSd/LV end-diastolic volumes). The primary end point was a combined end point of death, LV assist device, or heart transplantation. RESULTS: During a median follow-up of 3.9 years, 79 (32%) patients reached the primary end point. Using univariable Cox regression, unadjusted QRSd was unrelated to CRT outcome ( P=0.116). In contrast, normalized QRSd was a strong predictor of survival (hazard ratio, 0.81 per 0.1 ms/mL; P=0.008). Women demonstrated higher normalized QRSd than men (0.62±0.17 versus 0.55±0.17 ms/mL; P=0.003) and showed better survival after CRT (hazard ratio, 0.52; P=0.018). A multivariable prognostic model included normalized QRSd together with age, atrial fibrillation, renal function, and heart failure cause, whereas sex, diabetes mellitus, strict left bundle branch block morphology, and LV end-diastolic volumes were expelled from the model. CONCLUSIONS: Normalization of QRSd to LV dimension improves prediction of survival after CRT implantation. In addition, sex-specific differences in CRT outcome might be attributed to the higher QRSd/LV end-diastolic volumes ratio that was found in selected women, indicating more conduction delay.

Cumulative anthracycline exposure and risk of cardiotoxicity; a Danish nationwide cohort study of 2440 lymphoma patients treated with or without anthracyclines.

Cardiotoxicity is a known risk of anthracycline treatment. However, the relative contribution of anthracyclines to the development of congestive heart failure (CHF), when included in a poly-chemotherapy regimen, is unclear. We examined cardiotoxicity in adult patients with diffuse large B-cell lymphoma and follicular lymphoma undergoing first-line immunochemotherapy from 2000-2012. In total, 2440 patients without previous heart disease were identified from the Danish Lymphoma Registry, of which 1994 (81·7%) were treated with anthracycline-containing chemotherapy [R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CHOEP (R-CHOP + etoposide)] and 446 (18·3%) were treated without anthracyclines (reference group). Compared to the reference group, the adjusted hazard ratio of CHF after 3-5 cycles of R-CHOP/CHOEP was 5·0 [95% confidence interval (CI) 1·4; 18·5], 6 cycles 6·8 (95% CI 2·0; 23·3) and >6 cycles 13·4 (95% CI 4·0; 45·0). The cumulative 5-year risk of CHF with all-cause mortality as competing risk was 4·6% after 3-5 cycles of R-CHOP/CHOEP, 4·5% after 6 and 7·9% after more than 6 cycles. Cumulative 5-year risk for patients treated without anthracyclines was 0·8%. Using anthracyclines in first-line lymphoma treatment increases risk of CHF in patients without previous history of heart disease. In particular, treatment with >6 cycles of R-CHOP/CHOEP is associated with a significant increase in CHF rate.

Delays in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction Patients Presenting With Cardiogenic Shock.

OBJECTIVES: This study sought to examine whether quality improvement initiatives across multiple ST-segment elevation myocardial infarction (STEMI) systems translated to faster first medical contact (FMC)-to-device times for patients presenting with cardiogenic shock (CS). BACKGROUND: There are limited data describing contemporary rates of achieving guideline-directed FMC-to-device times for STEMI patients with CS. METHODS: From 2012 to 2014, the American Heart Association Mission: Lifeline STEMI Systems Accelerator project established a protocol-guided approach to STEMI reperfusion systems in 484 U.S. hospitals. The study was stratified by CS versus no CS at presentation and performed Cochrane-Armitage tests to evaluate trends of achieving FMC-to-device time targets. A multivariable logistic regression model assessed the association between achieving guideline-directed FMC-to-device times and mortality. RESULTS: Among 23,785 STEMI patients, 1,993 (8.4%) experienced CS at presentation. For direct presenters, patients with CS were less likely to achieve the 90-min FMC-to-device time compared with no-CS patients (37% vs. 54%; p < 0.001). For transferred patients, CS patients were even less likely to reach the 120-min FMC-to-device time compared with no-CS patients (34% vs. 47%; p < 0.0001). The Accelerator intervention did not result in improvements in the FMC-to-device times for direct-presenting CS patients (p for trend = 0.53), although there was an improvement for transferred patients (p for trend = 0.04). Direct-presenting patients arriving within 90 min had lower mortality rates compared with patients who reached after 90 min (20.49% vs. 39.12%; p < 0.001). CONCLUSIONS: Fewer than 40% of STEMI patients presenting with CS achieved guideline-directed FMC-to-device targets; delays in reperfusion for direct-presenting patients were associated with higher mortality.

Risk Prediction of Atrial Fibrillation Based on Electrocardiographic Interatrial Block.

BACKGROUND: The electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person. METHODS AND RESULTS: Digital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P-wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P-waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose-response relationship between the number of biphasic P-waves in inferior leads and the hazard of AF during follow-up. Discrimination of the 10-year outcome of AF, measured by time-dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43-1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40-1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10-year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P-wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB. CONCLUSIONS: IAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high-risk subgroups.

Association of Public Health Initiatives With Outcomes for Out-of-Hospital Cardiac Arrest at Home and in Public Locations.

Importance: Little is known about the influence of comprehensive public health initiatives according to out-of-hospital cardiac arrest (OHCA) location, particularly at home, where resuscitation efforts and outcomes have historically been poor. Objective: To describe temporal trends in bystander cardiopulmonary resuscitation (CPR) and first-responder defibrillation for OHCAs stratified by home vs public location and their association with survival and neurological outcomes. Design, Setting, and Participants: This observational study reviewed 8269 patients with OHCAs (5602 [67.7%] at home and 2667 [32.3%] in public) for whom resuscitation was attempted using data from the Cardiac Arrest Registry to Enhance Survival (CARES) from January 1, 2010, through December 31, 2014. The setting was 16 counties in North Carolina. Exposures: Patients were stratified by home vs public OHCA. Public health initiatives to improve bystander and first-responder interventions included training members of the general population in CPR and in the use of automated external defibrillators, teaching first responders about team-based CPR (eg, automated external defibrillator use and high-performance CPR), and instructing dispatch centers on recognition of cardiac arrest. Main Outcomes and Measures: Association of resuscitation efforts with survival and neurological outcomes from 2010 through 2014. Results: Among home OHCA patients (n = 5602), the median age was 64 years, and 62.2% were male; among public OHCA patients (n = 2667), the median age was 68 years, and 61.5% were male. After comprehensive public health initiatives, the proportion of patients receiving bystander CPR increased at home (from 28.3% [275 of 973] to 41.3% [498 of 1206], P < .001) and in public (from 61.0% [275 of 451] to 70.5% [424 of 601], P = .01), while first-responder defibrillation increased at home (from 42.2% [132 of 313] to 50.8% [212 of 417], P = .02) but not significantly in public (from 33.1% [58 of 175] to 37.8% [93 of 246], P = .17). Survival to discharge improved for arrests at home (from 5.7% [60 of 1057] to 8.1% [100 of 1238], P = .047) and in public (from 10.8% [50 of 464] to 16.2% [98 of 604], P = .04). Compared with emergency medical services-initiated CPR and resuscitation, patients with home OHCA were significantly more likely to survive to hospital discharge if they received bystander-initiated CPR and first-responder defibrillation (odds ratio, 1.55; 95% CI, 1.01-2.38). Patients with arrests in public were most likely to survive if they received both bystander-initiated CPR and defibrillation (odds ratio, 4.33; 95% CI, 2.11-8.87). Conclusions and Relevance: After coordinated and comprehensive public health initiatives, more patients received bystander CPR and first-responder defibrillation at home and in public, which was associated with improved survival.

Electrocardiographic Preexcitation and Risk of Cardiovascular Morbidity and Mortality: Results From the Copenhagen ECG Study.

BACKGROUND: The majority of available data on the clinical course of patients with ventricular preexcitation in the ECG originates from tertiary centers. We aimed to investigate long-term outcomes in individuals from a primary care population with electrocardiographic preexcitation. METHODS AND RESULTS: Digital ECGs from 328 638 primary care patients were collected during 2001 to 2011. We identified 310 individuals with preexcitation (age range, 8-85 years). Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. The median follow-up time was 7.4 years (quartiles, 4.6-10.3 years). Compared with the remainder of the population, patients with preexcitation had higher adjusted hazards of atrial fibrillation (hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.07-4.70) and heart failure (HR, 2.11; 95% CI, 1.27-3.50). Subgroup analysis on accessory pathway location revealed a higher adjusted hazard of heart failure for a right anteroseptal accessory pathway (HR, 5.88; 95% CI, 2.63-13.1). There was no evidence of a higher hazard of death among individuals with preexcitation when looking across all age groups (HR, 1.07; 95% CI, 0.68-1.68). However, a statistically significant (P=0.01) interaction analysis (<65 versus ≥65 years) indicated a higher hazard of death for patients with preexcitation ≥65 years (HR, 1.85; 95% CI, 1.07-3.18). CONCLUSIONS: In this large ECG study, individuals with preexcitation had higher hazards of atrial fibrillation and heart failure. The higher hazard of heart failure seemed to be driven by a right anteroseptal accessory pathway. Among elderly people, we found a statistically significant association between preexcitation and a higher hazard of death.