Complex Congenital Heart Disease in the Adult.

Congenital heart disease (CHD), a heterogeneous group of structural abnormalities of the cardiovascular system, is the most frequent cause of severe birth defects. Related to improved pediatric outcomes, there are now more adults living with CHD, including complex lesions, than children. Adults with CHD are at high risk for complications related to their underlying anatomy and past surgical palliative interventions. Adults with CHD require close monitoring and proactive management strategies to improve outcomes.

Maternal chronic hypertension in women veterans.

OBJECTIVE: To describe the prevalence of maternal chronic hypertension (MCH), assess how frequently blood pressure is controlled before pregnancy among those with MCH, and explore management practices for antihypertensive medications (AHM) during the pre-pregnancy and pregnancy periods. DATA SOURCES, STUDY SETTING, AND STUDY DESIGN: We conducted a descriptive observational study using data abstracted from the Veterans Health Administration (VA) inclusive of approximately 11 million Veterans utilizing the VA in fiscal years 2010-2019. DATA COLLECTION/EXTRACTION METHODS: Veterans aged 18-50 were included if they had a diagnosis of chronic hypertension before a documented pregnancy in the VA EMR. We identified chronic hypertension and pregnancy with diagnosis codes and defined uncontrolled blood pressure as ≥140/90 mm Hg on at least one measurement in the year before pregnancy. Sensitivity models were conducted for individuals with at least two blood pressure measurements in the year prior to pregnancy. Multivariable logistic regression explored the association of covariates with recommended and non-recommended AHMs received 0-6 months before pregnancy and during pregnancy. PRINCIPAL FINDINGS: In total, 8% (3767/46,178) of Veterans with a documented pregnancy in VA data had MCH. Among 2750 with MCH meeting inclusion criteria, 60% (n = 1626) had uncontrolled blood pressure on at least one BP reading and 31% (n = 846) had uncontrolled blood pressure on at least two BP readings in the year before pregnancy. For medications, 16% (n = 437) received a non-recommended AHM during pregnancy. Chronic kidney disease (OR = 3.2; 1.6-6.4) and diabetes (OR = 2.3; 1.7-3.0) were most strongly associated with use of a non-recommended AHM during pregnancy. CONCLUSIONS: Interventions are needed to decrease the prevalence of MCH, improve preconception blood pressure control, and ensure optimal pharmacologic antihypertensive management among Veterans of childbearing potential.

Maternal and Pregnancy Outcomes Following Heart Transplantation in the United States.

BACKGROUND: Improved survival following heart transplantation (HT) has led to more recipients contemplating pregnancy, but data on outcomes are limited. OBJECTIVES: The authors used a national data set to investigate and describe outcomes of pregnancies and deliveries in the United States in HT recipients. METHODS: Diagnosis and procedure codes from the 2010-2020 Nationwide Readmissions Database identified delivery hospitalizations, history of HT, comorbid conditions, and outcomes. The authors compared rates of severe maternal morbidity (SMM), nontransfusion SMM, cardiovascular SMM (cSMM), and preterm birth from delivery hospitalization between HT recipients and no-HT recipients. The authors evaluated readmission to 330 days postpartum. Logistic and proportional hazard regressions were performed, adjusting for age, socioeconomic and facility characteristics, and clinical comorbidities. RESULTS: Among 19,399,521 deliveries, 105 were HT recipients. Compared with no-HT, HT recipients were at higher risk for all SMM (24.8% vs 1.7%), nontransfusion SMM (20.8% vs 0.7%), cSMM (7.3% vs 0.12%), and preterm birth (43.3% vs 8.2%), all P < 0.001. In adjusted analyses, HT recipients had 16-fold greater odds of SMM, 28-fold greater odds of nontransfusion SMM, 38-fold greater odds of cSMM, and 7-fold greater odds of preterm birth. HT recipients had higher morbidity rates during delivery hospitalization and higher readmission rates within 1 year following delivery (26.9% vs 3.8%; adjusted HR: 6.03 [95% CI: 3.73-9.75]). CONCLUSIONS: Delivery with history of HT is associated with significantly increased rates of SMM, preterm birth, and hospital readmission. These results provide data regarding pregnancy outcomes for use when counseling patients with HT history who are considering pregnancy or who are pregnant.

Utilization and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Hypertrophic Cardiomyopathy.

Background There is uncertainty about the appropriate use of primary prevention implantable cardioverter-defibrillators (ICDs) among older patients with hypertrophic cardiomyopathy. Methods and Results Patients with hypertrophic cardiomyopathy who received a primary prevention ICD between 2010 and 2016 were identified using the National Cardiovascular Data Registry ICD Registry. Trends in ICD utilization and patient characteristics were assessed over time. Using linked Centers for Medicare and Medicaid Service claims data, Cox proportional hazard models assessed factors associated with mortality and postdischarge hospitalization for cardiac arrest/ventricular arrhythmia. Of 5571 patients with hypertrophic cardiomyopathy, 1511 (27.1%) were ≥65 years old. ICD utilization increased over time in all age groups. There were no changes in the prevalence of risk factors for sudden cardiac death over time. The variables most strongly associated with postdischarge mortality were older age (adjusted hazard ratio (aHR) 1.80 [95% CI, 1.47-2.21]), New York Heart Association class (III/IV versus I/II aHR 2.17 [95% CI, 1.57-2.98]), and left ventricular ejection fraction (left ventricular ejection fraction ≤35% versus >50% aHR 2.34 [95% CI, 1.58-3.48]; left ventricular ejection fraction 36%-50% versus >50% aHR 2.98 [95% CI, 2.02-4.40]), while history of nonsustained ventricular tachycardia (aHR 2.38 [95% CI, 1.62-3.51]) and New York Heart Association class (III/IV versus I/II aHR 1.84 [95% CI, 1.22-2.78]) were strongly associated with hospitalization for ventricular arrhythmia/cardiac arrest. Conclusions Primary prevention ICD utilization in patients with hypertrophic cardiomyopathy increased over time, including among those ≥65 years old. Among older patients, the strongest risk factors for hospitalization for ventricular arrhythmia/cardiac arrest following ICD implantation were history of nonsustained ventricular tachycardia and New York Heart Association class.

Antihypertensives in Pregnancy.

Hypertensive disorders of pregnancy (HDP) can result in significant maternal morbidity and even mortality. Available data suggest that many antihypertensives can be safely used in pregnant patients, albeit with close supervision of parameters like fetal growth and amniotic fluid volume. This article summarizes current guidelines on the diagnosis and treatment of hypertension in pregnancy and provides an in-depth guide to the available safety and efficacy data for antihypertensives during pregnancy and postpartum.

Sonographic Evaluation of the Placenta in Fontan Patients: A Case Series.

Due to the advancements in pediatric cardiothoracic surgery and medical management, more individuals with congenital heart disease are reaching reproductive age. It is well established that individuals with Fontan circulation are at an increased risk for maternal and fetal adverse outcomes including maternal cardiovascular complications, hypertensive disorders of pregnancy, preterm birth, and fetal growth restriction. Early onset of poor placental health likely related to chronically elevated central venous pressure/low cardiac output inherited to Fontan circulation may play a role in the development of these outcomes. In this case series, we present second-trimester placental imaging findings and pregnancy outcomes of three individuals with Fontan circulation who delivered at a tertiary center in the Southeastern United States.

Prospective Observational Study of N-terminal Pro-Brain Natriuretic Peptide Levels in Obese and Nonobese Women during Pregnancy.

OBJECTIVE: N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, varies by body mass index (BMI) outside of pregnancy. This study aimed to determine whether obesity affects NT-proBNP levels in pregnancy. STUDY DESIGN: This was a prospective observational study of healthy pregnant people in the third trimester (3TM) and postpartum (PP). Patients were excluded if they had significant medical comorbidities or if their fetuses had anomalies, growth restriction or aneuploidy. NT-proBNP was measured at 28 weeks (3TM), predelivery (PD), 1 to 2 days PP (immediate postpartum [IPP]), and 4 to 6 weeks PP (delayed postpartum [DPP]). LogNT-proBNP levels were analyzed using linear mixed effects models, including BMI < or ≥30, time, and time-by-BMI interactions. RESULTS: Fifty-five people (28 [51%] with BMI ≥ 30 and 27 [49%] with BMI < 30) were enrolled. A greater proportion of obese than nonobese subjects developed hypertensive disorders of pregnancy (50 vs. 15%, p = 0.010) and obese patients had higher systolic blood pressures at all time points (p < 0.05). NT-proBNP levels (median [interquartile range] in pg/mL) were 18 (6-28) versus 26 (17-48) at 3TM, 16 (3-38) versus 43 (21-60) at PD, 58 (20-102) versus 63 (38-155) at IPP, and 33 (27-56) versus 23 (8-42) at DPP for obese compared with nonobese patients. In linear mixed effects models, logNT-proBNP was lower in obese patients at 3TM (ß = -0.89 [95% confidence interval, CI: -1.51, -0.26]) and PD (ß = -1.05 [95% CI: -1.72, -0.38]). The logNT-proBNP trends over time differed by BMI category, with higher values in obese patients at both PP time points compared with the 3TM (IPP ß = 1.24 [95% CI: 0.75, 1.73]; DPP ß = 1.08 [95% CI: 0.52, 1.63]), but only IPP for nonobese patients (ß = 0.87 [95% CI: 0.36, 1.38]). CONCLUSION: Obese patients had lower NT-proBNP levels than nonobese patients during pregnancy but not PP. The prolonged PP elevation in NT-proBNP in obese patients suggests that their PP cardiac recovery may be more prolonged. KEY POINTS: · NT-proBNP levels are lower in obese than nonobese patients during pregnancy.. · Levels remain elevated in obese, but not nonobese, patients up to 4 to 6 weeks' postpartum.. · A lower threshold for concern regarding NT-proBNP levels may be needed in obese pregnant people..

Instituting a Curriculum for Cardio-Obstetrics Subspecialty Fellowship Training.

Maternal mortality is rising in the United States, and cardiovascular disease is the leading cause. Adverse pregnancy outcomes such as preeclampsia and gestational diabetes heighten the risk of cardiovascular complications during pregnancy and the peripartum period and are associated with long-term cardiovascular risks. The field of cardio-obstetrics is a subspecialty within adult cardiology that focuses on the management of women with or at high risk for heart disease who are considering pregnancy or have become pregnant. There is growing recognition of the need for more specialists with dedicated expertise in cardio-obstetrics to improve the cardiovascular care of this high-risk patient population. Current recommendations for cardiovascular fellowship training programs accredited by the Accreditation Council for Graduate Medical Education involve establishing core competency in the knowledge of managing heart disease in pregnancy. However, little granular detail is available of what such training should entail, which can lead to knowledge gaps. Additionally, dedicated advanced subspecialty training in this area is not commonly offered. Multidisciplinary collaborative teams have been shown to improve outcomes in cardiac patients during pregnancy, and cardiovascular fellows-in-training interested in cardio-obstetrics should have the opportunity to participate in and contribute to a pregnancy heart team. In this document, we describe a proposed specialized cardio-obstetrics training pathway that could serve to adequately prepare trainees to competently and comprehensively care for women with cardiovascular disease before, during, and after pregnancy.

Comparison of severe maternal morbidity in pregnancy by modified World Health Organization Classification of maternal cardiovascular risk.

BACKGROUND: To compare rates of severe maternal morbidity (SMM) for pregnant patients with a cardiac diagnosis classified by the modified World Health Organization (mWHO) classification to those without a cardiac diagnosis. METHODS: This retrospective study using the 2015-2019 Nationwide Readmissions Database identified hospitalizations, comorbidities, and outcomes using diagnosis and procedure codes. The primary exposure was cardiac diagnosis, classified into low-risk (mWHO class I and II) and moderate-to-high-risk (mWHO class II/III, III, or IV). The primary outcome was SMM or death during the delivery hospitalization; secondary outcomes included cardiac-specific SMM during delivery hospitalizations and readmissions after the delivery hospitalization. RESULTS: A weighted national estimate of 14,995,122 delivery admissions was identified, including 46,541 (0.31%) with mWHO I-II diagnoses and 37,330 (0.25%) with mWHO II/III-IV diagnoses. Patients with mWHO II/III-IV diagnoses experienced SMM at the highest rates (22.8% vs 1.6% for no diagnosis; with adjusted relative risk (aRR) of 5.67 [95% CI: 5.36-6.00]). The risk of death was also highest for patients with mWHO II/III-IV diagnoses (0.3% vs <0.1% for no diagnosis; aRR 18.07 [95% CI: 12.25-26.66]). Elevated risk of SMM and death persisted to 11 months postpartum for those patients with mWHO II/III-IV diagnoses. CONCLUSIONS: In this nationwide database, SMM is highest among individuals with moderate-to-severe cardiac disease based on mWHO classification. This risk persists in the year postpartum. These results can be used to enhance pregnancy counseling.

Hypertensive Disorders of Pregnancy and Heart Failure Risk.

PURPOSE OF REVIEW: To review the data on hypertensive disorders of pregnancy (HDP) and heart failure (HF) risk. RECENT FINDINGS: Hypertensive disorders are the most common medical condition affecting women during pregnancy and are associated with future HF risk, including peripartum cardiomyopathy, pregnancy-associated HF with preserved ejection fraction, and new-onset HF later in life. HF related to HDP can occur during pregnancy and persist long term, as can be the case with peri-partum cardiomyopathy, or can develop years after delivery through mechanisms that have yet to be clearly defined. Unfortunately, the optimal ways to prevent HDP and its associated HF risks are unclear. Guidelines outlining appropriate risk stratification, coordination of postpartum medical care, and prevention of future cardiovascular disease among with HDP are urgently needed in order to decrease the risk of HF.

Pulmonary Hypertension in Adults with Congenital Heart Disease.

Pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) affects 5% to 10% of adults with CHD and is associated with significant morbidity and mortality. PAH-CHD develops as a consequence of intracardiac or extracardiac systemic-to-pulmonary shunts that lead to pulmonary vascular remodeling through a pathologic process that is similar to other causes of PAH. Eisenmenger syndrome is the most severe phenotype of PAH-CHD and is characterized by severe elevation in pulmonary vascular resistance, with shunt reversal causing hypoxemia and central cyanosis. The primary management strategy for most patients with PAH-CHD is medical therapy, although defect closure is considered in select cases.

Impact of Pre-Existing Ischemic Heart Disease on Severe Maternal Morbidity and Mortality During Delivery Hospitalizations.

BACKGROUND: The impact of pre-existing ischemic heart disease (IHD) on pregnancy is incompletely described. OBJECTIVES: The purpose of this study was to compare adverse pregnancy outcomes between those with IHD and those with a cardiac diagnosis categorized by the modified World Health Organization classification and those without a cardiac diagnosis. METHODS: This retrospective study used the 2015 to 2018 Nationwide Readmissions Database. Delivery hospitalizations, comorbidities, and outcomes were identified using diagnosis and procedure codes. The exposure was isolated IHD. The primary outcome was severe maternal morbidity (SMM) or death during the delivery hospitalization, analyzed using adjusted relative risk (aRR) regression and weighted to account for the Nationwide Readmissions Database's complex survey methods. RESULTS: Of 11,556,136 delivery hospitalizations, 65,331 had another cardiac diagnosis, and 3,009 had IHD alone. Patients with IHD were older and had higher rates of diabetes and hypertension. In unadjusted analyses, adverse outcomes were more common among patients with IHD alone than among patients with no cardiac disease and modified World Health Organization class I-II disease. After adjustment, patients with IHD alone were associated with a higher risk of SMM or death (aRR: 1.51; 95% CI: 1.19-1.92) than those without a cardiac disease. In comparison, the aRR was 1.90 (95% CI: 1.76-2.06) for WHO class I-II diseases and 5.87 (95% CI: 5.49-6.27) for WHO II/III-IV diseases. Nontransfusion SMM or death (aRR: 1.60; 95% CI: 1.11-2.30) and cardiac SMM or death (aRR: 2.98; 95% CI: 1.75-5.08) were also higher for those with IHD. CONCLUSIONS: Isolated IHD in pregnancy is associated with worse outcomes than no cardiac disease during delivery hospitalization and approximates the risk associated with WHO I-II diagnoses.

Peripartum Cardiomyopathy.

IMPORTANCE: Peripartum cardiomyopathy is a rare form of heart failure due to left ventricular systolic dysfunction that affects women late in pregnancy and the postpartum period. A diagnosis of exclusion, peripartum cardiomyopathy can be difficult to diagnose in the context of the normal physiologic changes of pregnancy and requires a high index of suspicion. EVIDENCE ACQUISITION: Original research articles, review articles, and guidelines on peripartum cardiomyopathy were reviewed. RESULTS: The etiology of peripartum cardiomyopathy remains poorly defined, but theories include genetic predisposition, as well as myocardial inflammation and angiogenic dysregulation. Risk factors for this condition include hypertensive disorders of pregnancy, Black race, and maternal age older than 30 years. Patients with peripartum cardiomyopathy are at increased risk of acute clinical decompensation, cardiac arrhythmias, thromboembolic complications, and death. Primary treatment modalities include initiation of a medication regimen aimed at the optimization of preload and reduction of afterload. Maternal clinical status is the primary determinant for timing of delivery. CONCLUSIONS: Prompt diagnosis and medical management by an interdisciplinary care team are vital for improving outcomes in patients with peripartum cardiomyopathy.

Neurologic complications of congenital heart disease in adults.

Congenital heart disease (CHD) is a heterogeneous group of structural abnormalities of the cardiovascular system that are present at birth. Advances in childhood medical and surgical treatment have led to increasing numbers of adults with CHD. Neurological complications of CHD in adults are varied and can include an increased risk of stroke not only related to the underlying congenital defect and its surgical management but also due to atherosclerotic disease associated with advancing age. In addition to cerebrovascular events, CHD in adults is also associated with an increased risk of neurodevelopmental disorders, cognitive impairment, psychiatric disease, and epilepsy. Collaborative multidisciplinary care with contributions from neurologists and cardiologists with expertise in adult CHD is necessary to provide optimal long-term care for this complex and rapidly evolving population.

Implantable Cardioverter Defibrillator Utilization and Mortality Among Patients ≥65 Years of Age With a Low Ejection Fraction After Coronary Revascularization.

The purpose of this analysis was to assess implantable cardioverter-defibrillator (ICD) utilization and its association with mortality among patients ≥65 years of age after coronary revascularization. Patients in the National Cardiovascular Database Registry Chest Pain-Myocardial Infarction (MI) Registry who presented with MI from January 2, 2009 to December 31, 2016, had a left ventricular ejection fraction ≤35% and underwent in-hospital revascularization (10,014 percutaneous coronary intervention (PCI) and 1,647 coronary artery bypass grafting (CABG)) were linked with Medicare claims to determine rates of 1-year ICD implantation. The association between ICD implantation and 2-year mortality was assessed. Of 11,661 included patients, an ICD was implanted in 1,234 (10.6%) within 1 year of revascularization (1,063 (10.6%) PCI and 171 (10.4%) CABG). Among PCI-treated patients, in-hospital ventricular arrhythmia (adjusted hazard ratio [aHR] 1.60, 95% confidence interval [CI] 1.34 to 1.92), 2-week cardiology follow-up (aHR 1.48, 95% CI 1.29 to 1.70), readmission for heart failure (aHR 3.21, 95% CI 2.73 to 3.79), and readmission for MI (aHR 2.18, 95% CI 1.66 to 2.85) were positively associated with ICD implantation. Among CABG-treated patients, in-hospital ventricular arrhythmia (aHR 2.33, 95% CI 1.39 to 3.91), and heart failure readmission (aHR 3.14, 95% CI 1.96 to 5.04) were positively associated with ICD implantation. Women were less likely to receive an ICD, regardless of the revascularization strategy. ICD implantation was associated with lower 2-year all-cause mortality (aHR 0.74, 95% CI 0.63 to 0.86). In conclusion, only 1 in 10 Medicare patients with low ejection fraction received an ICD within 1 year after revascularization. Contact with the healthcare system after discharge was associated with higher likelihood of ICD implantation. ICD implantation was associated with lower mortality following revascularization for MI.

Increased Risk of Aortic Dissection Associated With Pregnancy in Women With Turner Syndrome: A Systematic Review.

IMPORTANCE: Turner syndrome (TS) is one of the most common chromosomal abnormalities in women. The condition is characterized by gonadal dysgenesis and is associated with structural cardiac abnormalities. Assisted reproductive technology with oocyte donation may be successful but places women with TS at increased risk of aortic dissection and death. OBJECTIVE: To summarize all cases of aortic dissection associated with pregnancy in women with TS and provide guidance regarding the safety of pregnancy. EVIDENCE ACQUISITION: Systematic review of PubMed for reports of women with TS, aortic dissection, and pregnancy. RESULTS: There are 14 total reported cases of aortic dissection associated with pregnancy in women with TS. Ten of these cases occurred during pregnancy or in the first month postpartum. The majority of affected pregnancies resulted from oocyte donation, 2 of which were multiple gestations. Two women had a documented history of hypertension, and 3 pregnancies were complicated by preeclampsia. Bicuspid aortic valve and coarctation of the aorta were the most common associated cardiac anomalies. More than half of women had some degree of aortic dilatation. Two women had no identifiable risk factors. CONCLUSIONS AND RELEVANCE: Women with TS who desire pregnancy must be thoroughly counseled regarding the increased risk of aortic dissection during pregnancy and postpartum. Preconception consultation with maternal-fetal medicine, reproductive endocrinology, and cardiology is necessary along with a comprehensive physical evaluation. If women with TS choose to pursue pregnancy, they require rigorous cardiac monitoring each trimester during pregnancy and postpartum.

Causes of Death and Cardiovascular Comorbidities in Adults With Congenital Heart Disease.

Background Little is known about the contemporary mortality experience among adults with congenital heart disease (CHD). The objectives of this study were to assess the age at death, presence of cardiovascular comorbidities, and most common causes of death among adults with CHD in a contemporary cohort within the United States. Methods and Results Patients with CHD who had a healthcare encounter between 2008 and 2013 at 1 of 5 comprehensive CHD centers in North Carolina were identified by International Classification of Diseases, Ninth Revision (ICD-9), code. Only patients who could be linked to a North Carolina death certificate between 2008 and 2016 and with age at death ≥20 years were included. Median age at death and underlying cause of death based on death certificate data were analyzed. The prevalence of acquired cardiovascular risk factors was determined from electronic medical record data. Among the 629 included patients, the median age at death was 64.2 years. Those with severe CHD (n=157, 25%), shunts (n=202, 32%), and valvular lesions (n=174, 28%) had a median age at death of 46.0, 65.0, and 73.3 years, respectively. Cardiovascular death was most common in adults with severe CHD (60%), with 40% of those deaths caused by CHD. Malignancy and ischemic heart disease were the most common causes of death in adults with nonsevere CHD. Hypertension and hyperlipidemia were common comorbidities among all CHD severity groups. Conclusions The most common underlying causes of death differed by lesion severity. Those with severe lesions most commonly died from underlying CHD, whereas those with nonsevere disease more commonly died from non-CHD causes.

Future research prioritization in cardiac resynchronization therapy.

BACKGROUND: Although cardiac resynchronization therapy (CRT) is effective for some patients with heart failure and a reduced left ventricular ejection fraction (HFrEF), evidence gaps remain for key clinical and policy areas. The objective of the study was to review the data on the effects of CRT for patients with HFrEF receiving pharmacological therapy alone or pharmacological therapy and an implantable cardioverter-defibrillator (ICD) and then, informed by a diverse group of stakeholders, to identify evidence gaps, prioritize them, and develop a research plan. METHODS: Relevant studies were identified using PubMed and EMBASE and ongoing trials using clinicaltrials.gov. Forced-ranking prioritization method was applied by stakeholders to reach a consensus on the most important questions. Twenty-six stakeholders contributed to the expanded list of evidence gaps, including key investigators from existing randomized controlled trials and others representing different perspectives, including patients, the public, device manufacturers, and policymakers. RESULTS: Of the 18 top-tier evidence gaps, 8 were related to specific populations or subgroups of interest. Seven were related to the comparative effectiveness and safety of CRT interventions or comparators, and 3 were related to the association of CRT treatment with specific outcomes. The association of comorbidities with CRT effectiveness ranked highest, followed by questions about the effectiveness of CRT among patients with atrial fibrillation and the relationship between gender, QRS morphology and duration, and outcomes for patients either with CRT plus ICD or with ICD. CONCLUSIONS: Evidence gaps presented in this article highlight numerous, important clinical and policy questions for which there is inconclusive evidence on the role of CRT and provide a framework for future collaborative research.

Sex differences in left ventricular electrical dyssynchrony and outcomes with cardiac resynchronization therapy.

BACKGROUND: Women seem to derive more benefit from cardiac resynchronization therapy (CRT) than men, even after accounting for the higher burden of risk factors for nonresponse often observed in men. OBJECTIVE: To assess for sex-specific differences in left ventricular (LV) electrical dyssynchrony as a contributing electrophysiological explanation for the greater degree of CRT benefit among women. METHODS: We compared the extent of baseline LV electrical dyssynchrony, as measured by the QRS area (QRSA), among men and women with left bundle branch block (LBBB) undergoing CRT at Duke University (n = 492, 35% women) overall and in relation to baseline QRS characteristics using independent sample t tests and Pearson correlation coefficients. Cox regression analyses were used to relate sex, QRSA, and QRS characteristics to the risk of cardiac transplantation, LV assist device implant, or death. RESULTS: Although the mean QRS duration (QRSd) did not differ by sex, QRSA was greater for women vs men (113.8 µVs vs 98.2 µVs, P < .001), owing to differences in the QRSd <150 ms subgroup (92.3 ± 28.7 µVs vs 67.6 ± 26.2 µVs, P < .001). Among those with nonstrict LBBB, mean QRSd was similar but QRSA was significantly greater among women than men (96.0 ± 25.0 µVs vs 63.6 ± 26.2 µVs, P < .001). QRSA was similar among men and women with strict LBBB (P = .533). Female sex was associated with better long-term outcomes in an unadjusted model (hazard ratio 0.623, confidence interval 0.454-0.857, P = .004) but sex no longer predicted outcomes after accounting for differences in QRSA. CONCLUSIONS: Our study suggests that sex-specific differences in LV dyssynchrony contribute to greater CRT benefit among women. Standard QRSd and morphology assessments seem to underestimate the extent of LV electrical dyssynchrony among women with LBBB.