Brady, Peter A.

ABSTRACTBackgroundLate gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is a well‐established indicator of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). However, its association with electrocardiographic (ECG) abnormalities and the risk of atrial fibrillation (AF) remains uncertain.ObjectivesTo investigate the association between the presence and burden of LGE with ECG characteristics, including precordial voltage, depolarization and repolarization abnormalities, and the incidence of AF in adults with HCM.MethodsWe conducted a retrospective cohort study of 144 adults with HCM with CMR and 12‐lead ECG within 30 days of each other. LGE was quantified as a percentage of LV mass and categorized as absent, < 5%, or ≥ 5%. ECG parameters, including QRS voltage, repolarization abnormalities, and LVH criteria, were analyzed. Incident AF was assessed during a median follow‐up of 6.6 years.ResultsLGE was present in 96 (67%) patients, with 21 (22%) having ≥ 5% LGE. There were no significant differences in precordial voltage between patients with and without LGE across Sokolow‐Lyon, Cornell, and Romhilt‐Estes criteria. However, T‐wave inversion was more common in leads I (41% vs. 19%, p = 0.009), aVL (50% vs. 31%, p = 0.033), and V4 (41% vs. 23%, p = 0.035) in patients with LGE. Patients with ≥ 5% LGE had a significantly lower median LVEF (64% vs. 74%, p = 0.003). Additionally, LGE presence was not associated with an increased risk of incident AF (HR 1.8, 95% CI 0.6–5.3, p = 0.308).ConclusionIn contrast to pediatric HCM, LGE is associated with specific ECG repolarization abnormalities, particularly T‐wave inversion in lateral leads, but does not significantly affect precordial voltage in adults.

Background: Cardiac amyloidosis (CA) is associated with sinus node dysfunction (SND) and conduction system disease (CSD) yet data on pacing indications and outcomes is scarce. Methods: Retrospective review of patients (pts) with CA who had device implantation due to pacing indication at our institution. Results: At total of 51 (mean age 67.2±9.2 years, 90.2% male) pts with immunoglobulin light chain (n=27, 52.9%), hereditary transthyretin (n=7, 13.7%) and wild-type transthyretin (n=17, 33.3%) CA were included. Indication for pacing was exercise intolerance (n=16, 31.4%), syncope (n=16, 31.4%), congestive heart failure (n=5, 9.8%) and palpitation (n=2, 3.9%) with SND (n=23, 45.1%), CSD (17=33.3%) and uncontrolled atrial fibrillation (n=11, 21.6%). 16 (31.4%) pts received defibrillators (ICD) for primary prevention, of whom 8 (15.7%) had left ventricular ejection fraction (LVEF) ≤35%. Atrial (P wave: 1.7±1.2mV, threshold: 1.1±0.5mV/0.5±0.2ms) and right ventricular (RV) (R wave: 7.9±3.8mV, threshold: 0.8±0.4mV/0.4±0.1ms) lead parameters were satisfactory at implantation. During follow-up (mean 36.6±33.6 months), 26 (51%) pts reported symptomatic improvement (SI). Syncope was the only predictor of SI (OR 16.4, 95%CI 1.8-145.2, p=0.01) while exercise intolerance was not (OR 0.09, 95%CI 0.02-0.44, p=0.003). First-time life-threatening ventricular arrhythmias (VA) occurred in 6 (11.8%) pts, 3 (5.9%) had ICD implanted for LVEF ≤35%, 3 (5.9%) without ICD and LVEF ≥35%. Syncope was not predictive of first-time VA. RV lead noise led to inappropriate ICD shocks in 1 patient. Atrial lead sensing failure occurred in 6 (11.8%) and loss of capture in 5 (9.8%). Conclusion: Device implantation in patients with cardiac amyloidosis is safe but atrial lead failure is common. Syncope usually improves with pacing whereas other factors should be considered in those presented with exercise intolerance. Selection of pts who need pacing for prophylactic ICD implantation is challenging as neither left ventricular ejection fraction nor syncope are predictive of arrhythmic events.

Background Little is known about the effects of permanent transvenous device leads on bioprosthetic tricuspid valve (BTV) function. Hypothesis The goal of this study was to test the hypothesis that transvalvular device leads promote clinically significant BTV regurgitation. Methods A retrospective review of 58 patients who underwent BTV implantation and subsequently required endocardial pacemaker (n=52) or defibrillator (n=6) lead implantation through the BTV was conducted. Patient and prosthesis characteristics, lead type, and clinical events were collected. The incidence and severity of prosthetic tricuspid regurgitation (TR), determined by Doppler echocardiography, was compared to 265 patients who underwent BTV implantation without undergoing subsequent transvalvular device lead implantation. Results Over a mean follow up of 25 months, 5 patients (9%) with a transvalvular lead developed ≥ moderate prosthetic TR compared to 12 patients (5%) in the control group (P = 0.20). Kaplan Meier survival analysis revealed no significant difference in the incidence of TR in BTV patients with and without transvalvular leads (p = 0.45). Clinically significant prosthetic TR in patients with and without a transvalvular lead more commonly occurred 2 years or later after lead implantation or BTV implantation (4/5, 80% and 10/12, 83%). Conclusions Compared to BTV controls, there was no significant difference in the incidence of ≥ moderate prosthetic TR in patients with a transvalvular pacemaker or defibrillator lead (p = 0.45). Transvalvular lead implantation appears to be an acceptable approach for patients with a BTV who require permanent pacemaker or defibrillator placement.

Background Sarcoidosis is an inflammatory, noncaseating, granulomatous disorder of unknown cause that can affect any body system and is associated with cardiovascular disease including sudden cardiac death (SCD). Cardiac involvement in sarcoidosis is associated with higher risk of SCD, but the SCD risk in the general sarcoidosis population is unknown. We aimed to determine the risk of SCD in people with sarcoidosis versus the matched general population. Methods and Results A population‐based cohort of sarcoidosis and age‐ and sex‐matched comparators from January 1, 1976 to December 31, 2013 was used; presence of other comorbidities in the comparator group was not an exclusion criterion. Mortality, including time, place, and cause of death were measured and manually adjudicated for SCD events. Incidence rates are reported per 100 000 person‐years, and Cox models were used for group comparisons. Of the 345 incident cases of sarcoidosis (171 men; 50%) there were 58 reported deaths; 10 were definite/probable SCD versus 57 all‐cause and 9 SCDs in comparators. Median follow‐up was 12.9 years (interquartile range, 6.0–23.4 years) . Incidence rate of SCD in sarcoidosis was 192 (95% CI, 92–352) versus 155 (95% CI, 71–294) in comparators (hazard ratio [HR], 1.28 (95% CI, 0.52–3.17). Nocturnal deaths were more frequent in sarcoidosis 57 (95% CI, 12–168) versus 17 (95% CI, 0.4–95) (HR, 3.76 [95% CI, 0.39–36.47]). No significant differences were detected between the groups by sex, age, calendar year of diagnosis, or disease duration. Conclusions In a population‐based cohort of patients with sarcoidosis, the risk for SCD compared with matched comparators was not increased. There were more nocturnal deaths among patients with sarcoidosis, yet this was statistically insignificant.

Background: It is known that hypokalemia, hypocalcemia and hypomagnesemia cause a prolonged QTc interval and are associated with an increased risk of ventricular arrhythmias. However, there are limited data on optimal serum electrolytes for patients admitted to the coronary care unit (CCU). Objective: Here, we aimed to evaluate the relationship between serum potassium, ionized calcium and magnesium levels and in-hospital mortality in the CCU setting. Methods: This retrospective cohort study included 8,498 consecutive patients admitted to the CCU at an academic tertiary medical center from 2004 through 2013. The mean of serum electrolytes was categorized as <3.5, 3.5-<4.0, 4.0-<4.5 (reference), 4.5-<5.0, and ≥5.0 mEq/L for potassium; <4.4, 4.4-<4.6, 4.6-<4.8, 4.8-<5.0 (reference), and ≥5.0 mg/dL for ionized calcium; and <1.8, 1.8-<2.0, 2.0-<2.2 (reference), 2.2-<2.4, and ≥2.4 mg/dL for magnesium. Multivariate logistic regression analysis was used to determine the association between the mean of serum electrolytes and in-hospital mortality. Results: Of the 8,498 patients, 599 (7%) died during hospitalization. Relationship between mean serum potassium (U-shaped), ionized calcium (inverted J-shape) and magnesium (J-shaped) and in-hospital mortality was present in Figure. Serum potassium levels <3.5, 4.5-<5.0 and ≥5.0 mEq/L were independently associated with an increased risk of in-hospital mortality (adjusted OR 1.7 95% CI 1.1-2.5, OR 1.7 95% CI 1.3-2.2, and OR 3.4 95% CI 2.4-4.8, respectively), compared to the reference group. As for serum ionized calcium, the levels of <4.4, 4.4-<4.6, and 4.6-<4.8 mg/dL independently increased risk of mortality (adjusted OR 3.0 95% CI 2.3-4.0, OR 2.0 95% CI 1.5-2.6, and OR 1.4 95% CI, 1.1-1.8, respectively). As for serum magnesium, an only level above 2.4 mg/dL was associated with an increased mortality risk (OR 1.6 95% CI, 1.1-2.2). Conclusions: In the CCU setting, serum potassium 3.5-<4.5 mEq/L, ionized calcium ≥5.0 mg/dL and magnesium <2.4 mg/dL are associated with the lowest in-hospital mortality. These findings do not support supratherapeutic repletion of potassium and magnesium.

The aim of this study was to identify the optimal echocardiographic measurement of aortic regurgitation (AR) in continuous flow left ventricular assist devices (LVAD) and determine risk factors and clinical implications of de novo AR. Echocardiographic images from consecutive patients who underwent LVAD implantation from February 2007 to March 2017 were reviewed. Severity of de novo AR was determined by vena contracta (VC). Preimplant clinical characteristics, LVAD settings at discharge, and outcomes including heart failure hospitalizations, all-cause mortality, and ventricular arrhythmias of patients with greater than or equal to moderate de novo AR were compared with those with mild or no AR. Among 219 patients, greater than or equal to moderate de novo AR occurred in 65 (29.7%). Left ventricular assist devices support duration was longer with greater than or equal to moderate AR than no or mild AR. In multivariable analysis, preimplant trivial AR and persistent aortic valve (AV) closure were independently associated with de novo AR. By time-varying covariate analysis, survival and freedom from cardiovascular events in greater than or equal to moderate AR were significantly worse (hazard ratio [HR] = 3.947, p < 0.001 and HR = 4.666, p < 0.001). In conclusion, de novo greater than or equal to moderate AR measured by VC increases risk of adverse events. Longer LVAD support duration, preimplant trivial AR, and a closed AV are associated with occurrence of greater than or equal to moderate de novo AR.

Introduction Multi-detector computed tomography (MDCT) is commonly used to identify pulmonary vein and left atrial anatomy prior to catheter ablation for atrial fibrillation (CAAF). Additionally, transesophageal echocardiography (TEE) is utilized to exclude left atrial/left atrial appendage thrombus (ICT). Whether MDCT alone can be used to exclude thrombus obviating the need for TEE is unknown. Methods All Pts referred for CAAF at Mayo Clinic between March 2004 and October 2006 were included. Clinical data (including CHADS score), 64 slice MDCT (non-ECG gated), TEE and intra-cardiac echocardiograph (ICE) were all performed and recorded. Image data was reviewed independently and blinded. The left atrial appendage (LAA) was defined as fully opacified or underfilled. An underfilled LAA was further interrogated using a region of interest over the filling defect and mean attenuation in Hounsfield Units (HU) were recorded. Results In total 400 Pts (mean age 56 ± 10 yrs; 76% male; EF 56 ± 10 % ) were included. 362 had no ICT by TEE nor filling defect by MDCT. 38 patients had an underfilled LAA in whom ICT was confirmed by TEE in 7. Sensitivity and specificity of MDCT for ICT was 100% and 92% respectively with a NPV of 100%. In 19 Pts with underfilled LAA’s, a mean LAA emptying velocity was found to be significantly reduced at 26 cm/s (6 – 61 cm/s). Those with a thrombus had a mean attenuation value below 70 HU. CHADS2 score was higher (2.0 versus 1.0) in Pts with LAA filling defect versus those without LAA filling defect. All Pts with confirmed thrombus were taking Warfarin. ICT was not seen in any Pts aged <52 yrs with CHADS score ≤1. Conclusions Sensitivity and specificity of MDCT for detection of LAA thrombus is high. LAA filling defects on MDCT correlate with low emptying velocities by TEE and low attenuation value in HU. These data would suggest that in the absence of MDCT filling defect, no further imaging is required. TEE should be utilized prior to CAAF to investigate MDCT filling defects. Multidetector Computed Tomography for the Detection of LAA Thrombus

Introduction Left ventricular non-compaction (LVNC) is a rare cardiomyopathy thought to result from intrauterine arrest of myocardial compaction which has been associated with and increased risk of sudden cardiac death (SCD). However, appropriate identification of at-risk individuals and risk-stratification is lacking, particularly in patients diagnosed during adulthood. We sought to identify high-risk patients wtih LVNC in order to guide therapy. Hypothesis That patients with decreased left ventricular ejection fraction (LVEF) would have worse outcomes than those with preserved left ventricular function. Methods We reviewed outcomes in all patients diagnosed with LVNC at Mayo Clinic between 2001 through 2006. Data were prospectively entered into a centralized database and retrospectively analyzed. Mortality was compared to age and sex matched population rates. Results A total of 80 patients were diagnosed with LVNC during this interval. After exclusion of pediatric patients (n = 21), 59 adult patients (62% male; age 46 ± 19 years, range 18–83) were analyzed. There were 4 deaths in this group (none due to stroke, mortality 18% at 2 years) during follow-up (mean 13.0 ± 13.5 months, range 0–52). Overall survival of patients with LVNC was worse than age and sex matched controls (Minnesota population p < 0.001). This was also noted in patients with LVEF > 35% (n = 35, p = 0.02). Overall LVEF was 41 ± 16% but was lower in patients who died compared to survivors (26 ± 10% vs. 42 ± 15%; Hazard ratio = 2.0 for a decrease in ejection fraction of 10%, p = 0.12). There were no deaths in patients with LVEF > 50% (n = 17). Conclusion Survival of adults with LVNC is worse than expected for age and sex. A decrease in ejection fraction is associated with increased risk of death in this population. These data suggest that patients diagnosed with LVNC and reduced LVEF may benefit from ICD implantation, whereas patients with a normal LVEF may be observed.

Introduction: Appropriate selection of patients (pts) with heart failure (HF) who may benefit from cardiac resynchronization therapy (CRT) is difficult. We sought to identify a clinical risk score to better risk stratify patients prior to CRT implantation. Methods: Pts undergoing CRT at Mayo Clinic from 2000 –2005 were included. Multiple clinical variables (age, gender, anemia (Hgb <10g/dL), RF (creatinine clearance ≤ 60ml/min/1.73m 2 ), hyponatremia (Na ≤130mEq/L), elevated BNP level (>500pg/ml), etiology, EF ≤20%, and advanced HF (NYHA functional class III–IV) were assessed with outcomes following CRT. Multivariate analysis was used to determine a clinical risk score. Results: A total of 496 patients (80% males) age 68 ± 12 years (62% ischemic cardiomyopathy, EF 22% ± 8%) were included. In univariate analysis relative risk (RR) was > 1 for RF (RR 1.8, CI 1.3–2.8; p = 0.002), anemia (RR 3.3, CI 1.8 –5.5; p = 0.001), hyponatremia (RR 3.4, CI 1.4 – 6.9; p = 0.008), elevated BNP (RR 2.9, CI 1.6 –5.7; p < 0.001), ischemic cardiomyopathy (ICM) (RR 1.8, CI 1.2–2.7; p < 0.002), EF ≤ 20% (RR 1.5, CI 1.0 –2.1; p = 0.033), and advanced HF (RR 2.5, CI 1.5– 4.9; p < 0.001). Following multivariate analysis RF, anemia, ICM, and advanced HF remained significant predictors of poor outcome (p >0.01 for all). Survival with 3 or more of these clinical risk factors was significantly worse than with less risk factors (p <0.01, Figure ). Conclusions: Pre-implant clinical risk factors including anemia, RF, ICM and advanced HF predict worse outcome following CRT with ≥3 variables predicting >2-fold increased risk of death or heart transplantation. These factors should be considered when selecting pts prior to CRT.

Background : Lipid lowering therapy reduces mortality in patients with both ischemic and nonischemic cardiomyopathies and recently has been shown to decrease ICD shocks. Radiofrequency ablation (RFA) of recurrent VT in patients with an ICD also reduces shocks following intervention. It is unclear if statin therapy after VT RFA will further impact ICD shock rates. Methods : All patients from 1993–2005 who underwent a RFA procedure for recurrent VT at the Mayo Clinic with an ICD were included. Patient records were extracted for medical and procedural details and all ICD interrogations were reviewed for VT recurrence and therapies. Results: 63 patients (age 62±15 years) were followed over 3.9±3.6 years. Comorbid diseases included: coronary artery disease 37(58%, 34 prior myocardial infarction), ARVD/C 6(10%), nonischemic dilated cardiomyopathy 7(11%), moderate-severe valve disease 14(22%), hypertension 34(54%), and hyperlipidemia 35(56%). Ejection fraction was <0.35 in 34(56%). VT was induced in all patients (LV 55 (LVOT 1), RV 8 (RVOT 3) with multiple inducible VTs in 21(33%). VT was noninducible after RFA in 39(62%) patients. Dismissal medications included: statins 19(30%), beta blockers 40(66%), ACE/ARB 37(61%), diuretics 34(55%), and digoxin 23(37%). 5-year overall survival was 63%(95% CI 55–71). Age, diabetes, and renal insufficiency were associated with increased post ablation mortality, with no medication improving survival. 5-year survival free of ICD shocks was 31%(95% CI 24–38). Only statin therapy at discharge was associated with a decreased risk of ICD shocks [5(26%) versus 26(59%), p=0.020]. 7 additional patients received statins during follow-up, but not at discharge, of these 5(71%) had shocks. Conclusion : Statin use at discharge in patients with an ICD undergoing RFA for refractory VT significantly reduced recurrent ventricular arrhythmias and ICD shocks. Although the mechanism underlying the effects of statins on arrhythmic recurrence early after RFA requires further study, these data support aggressive therapy of the underlying substrate responsible for the VT.