Percutaneous Left Atrial Appendage Occlusion Therapy: Past, Present, and Future

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is increasing in incidence and prevalence worldwide. AF significantly increases the risk of intracardiac thrombus formation and, if left untreated, ischemic stroke. In patients with nonvalvular AF (NVAF), the left atrial appendage (LAA) has been determined to be the source of thrombus development in 91% to 99% of cases. In this regard, oral anticoagulants (OACs) have become the standard treatment for stroke prevention in most patients with AF; however, OACs are associated with a risk of bleeding complications, and their efficacy depends on optimal patient compliance. Among alternative approaches to embolic stroke prevention, surgical LAA excision for stroke prevention for valvular AF was attempted as early as the late 1940s. LAA excision remains recommended in surgical guidelines for patients with NVAF requiring open-heart coronary bypass or valvular replacement/repair surgeries. However, owing to the traumatic/invasive nature and suboptimal outcomes of conventional surgical LAA intervention, clinical application of this approach is limited in current cardiology practice. Percutaneous LAA occlusion (LAAO) is increasingly being performed as an alternative to OAC for stroke prevention, particularly in patients with elevated bleeding risk. Substantial progress has been made in percutaneous LAAO therapy since its inception approximately 20 years ago. This article systematically reviews the literature leading to the development of LAAO and the evidence-based clinical experience supporting the application of this treatment strategy for NVAF, with a focus on recently published critical evaluations of US FDA and CE mark approved LAAO devices. Future perspectives regarding knowledge and technology gaps are also discussed, recognizing the many ongoing clinical trials that are likely to be transformative and the critical unanswered questions regarding LAAO therapy

Sex Differences in Quality of Life and Clinical Outcomes in Patients with Heart Failure

Background: Heart failure (HF) is generally associated with poor quality of life (QoL). Limited data are available characterizing health-related QoL (HRQL) in Chinese patients with HF. Methods: We used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to record QoL in 4082 patients with HF from China who were followed up over 12 months in the Heart Failure Registry of Patient Outcomes (HERO) study. Baseline HRQL and differences in QoL between women and men with heart failure were compared. We used multivariable Cox regression with adjustment for variables to assess the association between MLHFQ summary scores and a composite of all-cause mortality and HF hospitalization. Result: At baseline, the mean MLHFQ in the overall population was 42.9 ± 19.57; the scores for physical and emotional domains were 22.0 ± 8.69 and 8.66 ± 6.08, respectively. Women had a higher (poorer) MLHFQ summary score (44.27 ± 19.13) than men (41.63 ± 19.90) (P<0.001). Female patients also had higher MLHFQ physical and emotional scores than male patients (P<0.001). The specific scores of the questionnaire were higher in women than men. NYHA class was the strongest independent predictor of MLHFQ score (β=6.12 unit increment; P<0.001). Sex was not independently associated with higher MLHFQ scores after multivariable adjustments. The 12-month mortality in the overall cohort was 19.6%, the hospitalization rate was 24.4%, and the composite endpoint was 40.15%. A 10-point increase in MLHFQ score was associated with higher risk of mortality (female and male HRs=1.19 [95% CI 1.12–1.26]; P<0.001 and 1.18 [95% CI 1.12–1.24]; P<0.001, respectively) and composite outcomes (HRs=1.08 [95% CI 1.04–1.13]; P<0.001 and 1.11 [95% CI 1.07–1.14]; P<0.001, respectively). Females did not show a significant association between HRQL and hospitalization (HR=1.04 [95% CI 0.99–1.09]; P=0.107). Conclusion: Quality of life was largely poorer in women than men, but was similar between sexes in terms of physical burden and emotional limitation. HRQL is an independent predictor of all-cause death and HF hospitalization in patients with HF

Dyssynchrony Induced by Ventricular Preexcitation: A Risk Factor for the Development of Dilated Cardiomyopathy

Background: Significant left ventricular dysfunction may arise in right-sided accessory pathways with ventricular preexcitation in the absence of recurrent or incessant tachycardia. This has just been realized and not enough attention has been paid to it. Methods : In the last 7 years, we identified 12 consecutive children with a diagnosis of ventricular preexcitation–induced dilated cardiomyopathy. This report describes the clinical and echocardiographic characteristics of the patients before and after ablation. Results: Dyssynchronous ventricular contraction was observed by M-mode echocardiography and two-dimensional strain analysis in all patients. The basal and middle segments of the interventricular septum became thin and moved similarly to an aneurysm, with typical bulging during the end of systole. The locations of the accessory pathways were the right-sided septum ( n =5) and the free wall ( n =7). Left ventricular synchrony was obtained shortly after ablation. The left ventricular function recovered to normal and the left ventricular end-diastolic diameter decreased gradually during follow-up. Conclusions: A causal relationship between ventricular preexcitation and the development of dilated cardiomyopathy is supported by the complete recovery of left ventricular function and reversed left ventricular remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was thought to be the crucial mechanism. Ventricular preexcitation–induced dilated cardiomyopathy is an indication for ablation with a good prognosis

Comparison of Segmentation Algorithms for Detecting Myocardial Infarction Using Late Gadolinium Enhancement Magnetic Resonance Imaging

Objective: The aim of this study was to validate the accuracy of a new automatic method for scar segmentation and compare its performance with that of two other frequently used segmentation algorithms. Methods: Twenty-six late gadolinium enhancement cardiovascular magnetic resonance images of diseased hearts were segmented by the full width at half maximum (FWHM) method, the n standard deviations ( n SD) method, and our new automatic method. The results of the three methods were compared with the consensus ground truth obtained by manual segmentation of the ventricular boundaries. Results: Our automatic method yielded the highest Dice score and the lowest volume difference compared with the consensus ground truth segmentation. The n SD method produced large variations in the Dice score and the volume difference. The FWHM method yielded the lowest Dice score and the greatest volume difference compared with the automatic, 6SD, and 8SD methods, but resulted in less variation when different observers segmented the images. Conclusion: The automatic method introduced in this study is highly reproducible and objective. Because it requires no manual intervention, it may be useful for processing large datasets produced in clinical applications

Discovery of Digenic Mutation, KCNH2 c.1898A >C and JUP c.916dupA, in a Chinese Family with Long QT Syndrome via Whole-Exome Sequencing

Long QT syndrome (LQTS), which is caused by an ion channel–related gene mutation, is a malignant heart disease with a clinical course of a high incidence of ventricular fibrillation and sudden cardiac death in the young. Mutations in KCNH2 (which encodes potassium voltage-gated channel subfamily H member 2) are responsible for LQTS in many patients. Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing. The c.916dupA mutation in JUP (which encodes junction plakoglobin) is also discovered. Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy. The double mutation in the proband may help explain his severe clinical manifestations, such as sudden cardiac death at an early age. Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line, while the mutation in JUP came from his maternal line. The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias

The Temporal Relation between Cardiomyopathy and LBBB and Response to Cardiac Resynchronization Therapy: Case Series and Literature Review

Background: Left bundle branch block (LBBB)-induced cardiomyopathy has been proposed, but the association between LBBB and cardiac resynchronization therapy (CRT) response remains unclear and practical criteria for selecting CRT candidates are needed. Methods: One hundred and seventeen consecutive heart failure patients were reviewed, 24 of whom received CRT. Only two patients had a clear temporal relation between cardiomyopathy and LBBB. Results: Compared with the patient with “cardiomyopathy-induced LBBB,” the patient with “LBBB-induced cardiomyopathy” had higher left ventricular (LV) wall thickness, higher LV wall thickening rate, higher peak circumferential strain, and longer peak circumferential strain delay. The LV deformation patterns in the two patients were obviously distinct on cardiovascular magnetic resonance tissue tracking. During follow-up, the patient with LBBB-induced cardiomyopathy had a good response to CRT (LV ejection fraction 23 before CRT vs. 30% at 6 months vs. 29 at 12 months vs. 32% at 18 months; LV end-diastolic diameter 77 mm before CRT vs. 66 mm at 6 months vs. 62 mm at 12 months vs. 63 mm at 18 months), and the other patient had no response to CRT (LV ejection fraction 29 before CRT vs. 29% at 6 months vs. 26 at 12 months vs. 22% at 24 months; LV end-diastolic diameter 85 mm before CRT vs. 88 mm at 6 months vs. 85 mm at 12 months vs. 84 mm at 24 months). Conclusion: The temporal relation between cardiomyopathy and LBBB could be a determinant for CRT response. Cardiovascular magnetic resonance tissue tracking may be a useful tool to identify the chronological order and a principal consideration for selecting candidates for CRT. Larger prospective clinical trials are needed to study the prevalence of, time course of, and risk factors for LBBB-induced cardiomyopathy

Sex Differences in Primary and Secondary Prevention of Cardiovascular Disease in China

Background: Despite improvements in diagnostic and therapeutic interventions to combat cardiovascular disease (CVD) in recent decades, there are significant ongoing access gaps and sex disparities in prevention that have not been adequately quantified in China. Methods: A representative, cross-sectional, community-based survey of adults (aged ≥45 years) was conducted in 7 geographic regions of China between 2014 and 2016. Logistic regression models were used to determine sex differences in primary and secondary CVD prevention, and any interaction by age, education level, and area of residence. Data are presented as adjusted odds ratios (ORs) and 95% CIs. Results: Of 47 841 participants (61.3% women), 5454 (57.2% women) had established CVD and 9532 (70.5% women) had a high estimated 10-year CVD risk (≥10%). Only 48.5% and 48.6% of women and 39.3% and 59.8% of men were on any kind of blood pressure (BP)-lowering medication, lipid-lowering medication, or antiplatelet therapy for primary and secondary prevention, respectively. Women with established CVD were significantly less likely than men to receive BP-lowering medications (OR, 0.79 [95% CI, 0.65-0.95]), lipid-lowering medications (OR, 0.69 [95% CI, 0.56-0.84]), antiplatelets (OR, 0.53 [95% CI, 0.45-0.62]), or any CVD prevention medication (OR, 0.62 [95% CI, 0.52-0.73]). Women with established CVD, however, had better BP control (OR, 1.31 [95% CI, 1.14-1.50]) but less well-controlled low-density lipoprotein cholesterol (OR, 0.66 [95% CI, 0.57-0.76]), and were less likely to smoke (OR, 13.89 [95% CI, 11.24-17.15]) and achieve physical activity targets (OR, 1.92 [95% CI, 1.61-2.29]). Conversely, women with high CVD risk were less likely than men to have their BP, low-density lipoprotein cholesterol, and bodyweight controlled (OR, 0.46 [95% CI, 0.38-0.55]; OR, 0.60 [95% CI, 0.52-0.69]; OR, 0.55 [95% CI, 0.48-0.63], respectively), despite a higher use of BP-lowering medications (OR, 1.21 [95% CI, 1.01-1.45]). Younger patients (<65 years) with established CVD were less likely to be taking CVD preventive medications, but there were no sex differences by area of residence or education level. Conclusions: Large and variable gaps in primary and secondary CVD prevention exist in China, particularly for women. Effective CVD prevention requires an improved overall nationwide strategy and a special emphasis on women with established CVD, who have the greatest disparity and the most to benefit

Atrial Fibrillation Follow-up Investigation to Recover Memory and Learning Trial (AFFIRMING): Rationale and Design of a Multi-center, Double-blind, Randomized Controlled Trial

Background: People with atrial fibrillation (AF) have elevated risk of developing cognitive impairment. At present, there is a dearth of randomized controlled trials investigating cognitive impairment management in patients with AF. The Atrial Fibrillation Follow-up Investigation to Recover Memory and learning (AFFIRMING) study is aimed at evaluating the potential for computerized cognitive training to improve cognitive function in patients with AF. Methods: The study is a multi-center, double-blind, randomized controlled study using a 1:1 parallel design. A total of 200 patients with AF and mild cognitive decline without dementia are planned to be recruited. The intervention group will use the adaptive training software with changes in difficulty, whereas the positive control group will use basic training software with minimal or no variation in difficulty level. At the end of 12 weeks, the participants will be unblinded, and the positive control group will stop training. The intervention group will be rerandomized 1:1 to stop training or continue training. All participants will be followed up until 24 weeks. The primary endpoint is the proportion of the improvement of the global cognitive function at week 12 compared with baseline, using the Basic Cognitive Ability Test (BCAT)