Jonathan C. Hsu

Predictors of Super-Response to Cardiac Resynchronization Therapy and Associated Improvement in Clinical Outcome: The MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) Study

OBJECTIVES The authors investigated predictors of left ventricular ejection fraction (LVEF) super-response to cardiac resynchronization therapy with defibrillator (CRT-D) and whether super-response translated into improved event-free survival in patients with mildly symptomatic heart failure (HF). BACKGROUND Few data exist on predictors of super-response to CRT-D and associated morbidity and mortality in mildly symptomatic HF populations. METHODS Patients were assigned to CRT-D with paired echocardiograms at baseline and at 12 months (n = 752). Super-response was defined by the top quartile of LVEF change. Best-subset regression analysis identified predictors of LVEF super-response. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to investigate associations of response category with development of nonfatal HF event or all-cause death. RESULTS All 191 super-responders experienced an LVEF increase of ≥14.5% (mean LVEF increase 17.5 ± 2.7%). Six predictors were associated with LVEF super-response to CRT-D therapy: female sex (odds ratio [OR]: 1.96; p = 0.001), no prior myocardial infarction (OR: 1.80; p = 0.005), QRS duration ≥150 ms (OR: 1.79; p = 0.007), left bundle branch block (OR: 2.05; p = 0.006), body mass index <30 kg/m(2) (OR: 1.51; p = 0.035), and smaller baseline left atrial volume index (OR: 1.47; p < 0.001). Cumulative probability of HF or all-cause death at 2 years was 4% in super-responders, 11% in responders, and 26% in hypo-responders (log-rank p < 0.001 overall). In multivariate analysis, hyporesponse was associated with increased risk of HF or all-cause death, compared with super-response (hazard ratio: 5.25; 95% confidence interval: 2.01 to 13.74; p = 0.001). CONCLUSIONS Six baseline factors predicted LVEF super-response in CRT-D-treated patients with mild HF. Super-response was associated with reduced risk of subsequent cardiac events. (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk: Insights From the NCDR PINNACLE Registry

IMPORTANCE Patients with atrial fibrillation (AF) are at a proportionally higher risk of stroke based on accumulation of well-defined risk factors. OBJECTIVE To examine the extent to which prescription of an oral anticoagulant (OAC) in US cardiology practices increases as the number of stroke risk factors increases. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional registry study of outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registrys PINNACLE (Practice Innovation and Clinical Excellence) Registry between January 1, 2008, and December 30, 2012. As a measure of stroke risk, we calculated the CHADS2 score and the CHA2DS2-VASc score for all patients. Using multinomial logistic regression models adjusted for patient, physician, and practice characteristics, we examined the association between increased stroke risk score and prescription of an OAC. MAIN OUTCOMES AND MEASURES The primary outcome was prescription of an OAC with warfarin sodium or a non-vitamin K antagonist OAC. RESULTS The study cohort comprised 429 417 outpatients with AF. Their mean (SD) age was 71.3 (12.9) years, and 55.8% were male. Prescribed treatment consisted of an OAC (192 600 [44.9%]), aspirin only (111 134 [25.9%]), aspirin plus a thienopyridine (23 454 [5.5%]), or no antithrombotic therapy (102 229 [23.8%]). Each 1-point increase in risk score was associated with increased odds of OAC prescription compared with aspirin-only prescription using the CHADS2 score (adjusted odds ratio, 1.158; 95% CI, 1.144-1.172; P < .001) and the CHA2DS2-VASc score (adjusted odds ratio, 1.163; 95% CI, 1.157-1.169; P < .001). Overall, OAC prescription prevalence did not exceed 50% even in higher-risk patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4. CONCLUSIONS AND RELEVANCE In a large quality improvement registry of outpatients with AF, prescription of OAC therapy increased with a higher CHADS2 score and CHA2DS2-VASc score. However, a plateau of OAC prescription was observed, with less than half of high-risk patients receiving an OAC prescription.

Mitotic exit control of the Saccharomyces cerevisiae Ndr/LATS kinase Cbk1 regulates daughter cell separation after cytokinesis.

ABSTRACT Saccharomyces cerevisiae cell division ends with destruction of a septum deposited during cytokinesis; this must occur only after the structures construction is complete. Genes involved in septum destruction are induced by the transcription factor Ace2, which is activated by the kinase Cbk1, an Ndr/LATS-related protein that functions in a system related to metazoan hippo pathways. Phosphorylation of a conserved hydrophobic motif (HM) site regulates Cbk1; at peak levels in late mitosis we found that approximately 3% of Cbk1 carries this modification. HM site phosphorylation prior to mitotic exit occurs in response to activation of the FEAR (Cdc fourteen early anaphase release) pathway. However, HM site phosphorylation is not sufficient for Cbk1 to act on Ace2: the kinase is also negatively regulated prior to cytokinesis, likely by cyclin-dependent kinase (CDK) phosphorylation. Cbk1 cannot phosphorylate Ace2 until after mitotic exit network (MEN)-initiated release of the phosphatase Cdc14. Treatment of Cbk1 with Cdc14 in vitro does not increase its intrinsic enzymatic activity, but Cdc14 is required for Cbk1 function in vivo. Thus, we propose that Cdc14 coordinates cell separation with mitotic exit via FEAR-initiated phosphorylation of the Cbk1 HM site and MEN-activated reversal of mitotic CDK phosphorylations that block both Cbk1 and Ace2 function.

Predictors of an inadequate defibrillation safety margin at ICD implantation: insights from the National Cardiovascular Data Registry.

BACKGROUND Defibrillation testing is often performed to establish effective arrhythmia termination, but predictors and consequences of an inadequate defibrillation safety margin (DSM) remain largely unknown. OBJECTIVES The aims of this study were to develop a simple risk score predictive of an inadequate DSM at implantable cardioverter-defibrillator (ICD) implantation and to examine the association of an inadequate DSM with adverse events. METHODS A total of 132,477 ICD Registry implantations between 2010 and 2012 were analyzed. Using logistic regression models, factors most predictive of an inadequate DSM (defined as the lowest successful energy tested <10 J from maximal device output) were identified, and the association of an inadequate DSM with adverse events was evaluated. RESULTS Inadequate DSMs occurred in 12,397 patients (9.4%). A simple risk score composed of 8 easily identifiable variables characterized patients at high and low risk for an inadequate DSM, including (with assigned points) age <70 years (1 point); male sex (1 point); race: black (4 points), Hispanic (2 points), or other (1 point); New York Heart Association functional class III (1 point) or IV (3 points); no ischemic heart disease (2 points); renal dialysis (3 points); secondary prevention indication (1 point); and ICD type: single-chamber (2 points) or biventricular (1 point) device. An inadequate DSM was associated with greater odds of complications (odds ratio: 1.22; 95% confidence interval: 1.09 to 1.37; p = 0.0006), hospital stay >3 days (odds ratio: 1.24; 95% confidence interval: 1.19 to 1.30; p < 0.0001), and in-hospital mortality (odds ratio: 1.96; 95% confidence interval: 1.63 to 2.36; p < 0.0001). CONCLUSIONS A simple risk score identified ICD recipients at risk for an inadequate DSM. An inadequate DSM was associated with an increased risk for in-hospital adverse events.

Safety of radiofrequency catheter ablation without coronary angiography in aortic cusp ventricular arrhythmias

BACKGROUND Ventricular arrhythmias (VAs) originating from the aortic root are common. Coronary angiography is typically recommended before catheter ablation to document proximity of the ablation catheter to the coronary ostia. OBJECTIVE To investigate how often catheter ablation in the aortic root could be guided by phased-array intracardiac echocardiography (ICE) and electroanatomic mapping without requiring aortography or coronary angiography. METHODS We reviewed consecutive patients referred for aortic root VAs to operators experienced in the use of ICE at a single center. An ICE catheter and a 3.5-mm irrigated ablation catheter were used in all cases, and the need for angiography before ablation was documented. Acute success and acute and 30-day complications were noted. RESULTS Thirty-five patients (age 58 ± 13 years; 74% men) were referred for the ablation of VAs; 32 of 35 (91%) underwent ablation using ICE and 3-dimensional mapping without the need for coronary angiography. Successful acute ablation was achieved in 29 of 35 (83%) patients. In all cases, the catheter tip was directly visualized with ICE >1 cm from the coronary ostia. The site of origin of the earliest VA was the left cusp (17 of 35 [49%]), right cusp (9 of 35 [26%]), right-left cusp junction (8 of 35 [23%]), or right-noncoronary cusp junction (1 of 35 [3%]). There were no cases of coronary injury, embolic stroke, aortic root perforation, worsening of aortic regurgitation, or death acutely or at 30 days. CONCLUSION Radiofrequency ablation of VAs originating from the aortic root may be safely performed using ICE and electroanatomic mapping in the majority of cases without the need for coronary angiography.

Differences in accessory pathway location by sex and race

BACKGROUND The etiology of accessory pathway (AP) formation is generally unknown. OBJECTIVE The purpose of this study was to test the hypothesis that AP formation is genetically mediated by examining whether AP location differs by sex and/or race, using sex and race as proxies to distinguish genetically different individuals. METHODS This was a single-center, retrospective cohort study of 282 consecutive patients undergoing their first electrophysiology study that revealed at least one AP between 2004 and 2008. Sex and race were compared with AP location determined by invasive electrophysiology study. RESULTS Eighty-nine (52%) males and 40 (36%) females had a left posterior AP (P = .006). Sixty-four (57%) females had a right annular AP, compared with 55 (32%) males (P <.001). After adjusting for age and race, females had 2.8-fold greater odds of having a right annular AP compared with males (95% confidence interval [CI] 1.70-4.65 greater odds; P <.001). While right anterior (free-wall) pathways were rare in all other races (12%), a significantly larger proportion of Asians (n = 10, 26%) had a right anterior AP (P = .017). After adjusting for sex and age, Asians had 3.8-fold greater odds of having a right anterior AP compared with other races (95% CI 1.5-9.4 greater odds; P = .004). CONCLUSIONS Females more commonly had right annular APs, and Asians had right anterior APs substantially more frequently than other races. These findings suggest that the pathogenesis of AP formation may have a genetic component.

Randomized trial of conventional transseptal needle versus radiofrequency energy needle puncture for left atrial access (the TRAVERSE-LA study).

Background Transseptal puncture is a critical step in achieving left atrial (LA) access for a variety of cardiac procedures. Although the mechanical Brockenbrough needle has historically been used for this procedure, a needle employing radiofrequency (RF) energy has more recently been approved for clinical use. We sought to investigate the comparative effectiveness of an RF versus conventional needle for transseptal LA access. Methods and Results In this prospective, single‐blinded, controlled trial, 72 patients were randomized in a 1:1 fashion to an RF versus conventional (BRK‐1) transseptal needle. In an intention‐to‐treat analysis, the primary outcome was time required for transseptal LA access. Secondary outcomes included failure of the assigned needle, visible plastic dilator shavings from needle introduction, and any procedural complication. The median transseptal puncture time was 68% shorter using the RF needle compared with the conventional needle (2.3 minutes [interquartile range {IQR}, 1.7 to 3.8 minutes] versus 7.3 minutes [IQR, 2.7 to 14.1 minutes], P=0.005). Failure to achieve transseptal LA access with the assigned needle was less common using the RF versus conventional needle (0/36 [0%] versus 10/36 [27.8%], P<0.001). Plastic shavings were grossly visible after needle advancement through the dilator and sheath in 0 (0%) RF needle cases and 12 (33.3%) conventional needle cases (P<0.001). There were no differences in procedural complications (1/36 [2.8%] versus 1/36 [2.8%]). Conclusions Use of an RF needle resulted in shorter time to transseptal LA access, less failure in achieving transseptal LA access, and fewer visible plastic shavings. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209260.

Utilization trends and clinical outcomes in patients implanted with a single- vs a dual-coil implantable cardioverter-defibrillator lead: Insights from the ALTITUDE Study.

BACKGROUND Historically, the most commonly implanted implantable cardioverter-defibrillator (ICD) lead is dual coil. Conventional wisdom holds that single-coil leads may be less effective than dual-coil leads, but easier to extract. No contemporary large-scale studies have evaluated the relative epidemiology of these 2 leads or compared their respective clinical outcomes. OBJECTIVE We sought to evaluate trends in single- vs dual-coil ICD lead implantation and differences in clinical outcomes. METHODS We evaluated 129,520 ICD recipients enrolled in the LATITUDE remote monitoring system between 2004 and 2014. Kaplan-Meier analyses and Cox proportional hazards regression analyses were used for univariate and multivariate survival analysis, respectively. RESULTS The majority of ICD recipients received a dual-coil lead (n = 110,330 [85.2%]). Single-coil lead implantation increased from 1.9% to 55.2% between 2004 and 2014. After adjusting for age, sex, device type, and year of implant, single-coil lead implantation was associated with a greater odds of induction for defibrillation testing (odds ratio 1.05; 95% confidence interval [CI] 1.01-1.09; P = .0274), a higher rate of lead being taken out of service (hazard ratio 1.19; 95% CI 1.06-1.33; P = .0032), and a decreased mortality rate (hazard ratio 0.91; 95% CI 0.87-0.96; P = .0004). In a 795 patient subset with adjudicated shock outcomes, first shock success was no different (87.0% in single coil vs 86.1% in dual coil; P = .8473). CONCLUSION In a large real-world US population, single-coil lead implantation rates increased substantially between 2004 and 2014. Single-coil lead implantation was associated with more frequent defibrillation testing and the lead being taken out of service, but was not associated with increased mortality or more frequent defibrillation failure.

Elevated pulmonary artery systolic pressures are associated with a lower risk of atrial fibrillation following lung transplantation

BACKGROUND Atrial fibrillation (AF) is common after open-chest procedures, but the etiology remains poorly understood. Lung transplant procedures allow for the study of novel contributing factors. METHODS Records of lung transplant procedures performed at a single center between 2002 and 2009 were reviewed. RESULTS Of 174 patients, 27 (16%) had AF a median 6 days post-surgery. Post-operative AF patients less often had right ventricular hypertrophy (RVH) by either electrocardiogram (0 versus 14%, P=.042) or echocardiography (19% versus 47%, P=.006), and had lower pulmonary artery systolic pressures (PASP) (39 ± 12 versus 51 ± 22, P=.005). After multivariable adjustment, every 10-mm Hg increase in PASP was associated with a 31% reduction in the odds of post-operative AF (OR 0.69, 95% CI 0.49-0.98, P=.035). A higher pulmonary pressure was the only predictor independently associated with less post-operative AF. CONCLUSIONS Higher PASP was associated with a lower risk of AF after lung transplantation.

Clinical and electrocardiographic characteristics of idiopathic ventricular arrhythmias with right bundle branch block and superior axis: Comparison of apical crux area and posterior septal left ventricle

BACKGROUND Right bundle branch block (RBBB) with superior axis electrocardiographic (ECG) morphology is common in patients with idiopathic ventricular arrhythmia (VA) originating from the left posterior fascicle (LPF), from the left ventricular (LV) posterior papillary muscles (PPM), and rarely from the cardiac apical crux. OBJECTIVE The purpose of this study was to describe the ECG and clinical characteristics of idiopathic VA presenting with RBBB and superior axis. METHODS We studied 40 patients who underwent successful catheter ablation of idiopathic VAs originating from the LPF (n = 18), LV PPM (n = 15), and apical crux (n = 7). We investigated clinical and ECG characteristics, including maximum deflection index and QRS morphology in leads aVR and V6. RESULTS Syncope was more frequently seen in apical crux VA compared with other VAs (57% vs 6%, P < .001). Patients with apical crux VA more frequently had an maximum deflection index ≥0.55 compared with LPF VA and PPM VA (P = .02). A monophasic R wave in aVR and QS or r/S ratio <0.15 in V6 (P < .001) could distinguish apical crux VA from other VAs with high accuracy. All patients with VA underwent attempted ablation in the endocardium (success rate: LPF 89%, PPM 80%, crux 14%). Only 1 of 7 patients with apical crux VA had acute success with ablation in the middle cardiac vein. In 2 of apical crux patients, epicardial ablation using subxiphoid approach was performed successfully. CONCLUSION We could distinguish LPF VA, PPM VA, and apical crux VA using a combination of clinical and ECG characteristics. These findings might be useful for counseling patients and planning an ablation strategy.