Citations

Introduction: Familial Hypercholesterolemia (FH) is a common inherited disorder of lipid metabolism. FH patients are at an increased risk of atherosclerotic cardiovascular disease (ASCVD) due to elevated low-density lipoprotein cholesterol (LDL-C) levels. Patients with FH may not reach target LDL-C levels despite maximally tolerated statin (±ezetimibe) therapy (MTT). The AHA scientific statement on FH highlighted the need for developing decision aids (DAs) to facilitate shared decision making (SDM) regarding additional therapy including PCSK9 inhibitors. Methods: A user-centered design process was initiated to understand FH treatment decisions and to develop prototype interventions. Patients with FH had their diagnosis confirmed by genetic testing. Encounters between FH patients and health care providers were video recorded and analyzed to assess how decisions are made regarding lipid lowering therapy. Nine encounters were recorded: 3 with a genetic counselor and 6 with an FH specialist. Informed by clinical encounters and literature review, we developed content for a DA related to available therapeutic options for FH patients on MTT. Results: A prototype online DA was created to support in-encounter discussion of a patient’s risk of adverse cardiovascular events and which therapies may be best suited to the patient (Figure). 5 and 10-year ASCVD risk is estimated using the SAFEHEART Risk Score (SRS). Risk is communicated in numbers using a 100-person icon array and the language “Out of 100 persons like you...”. Therapeutic options include watchful waiting, bile acid sequestrants, and PCSK9 inhibitors. For each option, the degree of risk reduction, costs, and side effects are presented. The tool is currently being refined by analyzing additional encounters with FH patients. Conclusion: We developed an interactive prototype DA to facilitate SDM for FH patients on MTT. After further iterative testing the tool will be deployed in the electronic health record.

Introduction: Hypertrophic cardiomyopathy (HCM) is associated with excessive left ventricular (LV) hypertrophy (LVH), myocyte disarray and expansion of interstitial collagen. These factors alter mechanical properties of the myocardial tissue. Intrinsic velocity propagation (iVP) of myocardial stretch is a new validated measure of myocardial elasticity. Hypothesis: iVP in left ventricular (LV) myocardium of patients with HCM will be increased compared to normal subjects. Methods: We studied prospectively 100 subjects: 42 with HCM (age 57 ± 14 years; 79% with asymmetric septal LVH) and 58 normal controls without cardiovascular disease (age 48 ± 13 years). Patients had comprehensive transthoracic echocardiography and cardiac magnetic resonance imaging (MRI; n=29). iVP was measured throughout the LV myocardium during late diastole using ultra-high frame rate tissue Doppler imaging (350-460 fps) (6 LV walls, 3 standard apical views). Chamber stiffness (CS) was evaluated from end-diastolic pressure-volume relationship (EDPVR) estimated noninvasively by the single-beat method (EDP=αV β ). End-diastolic pressure (EDP) was estimated from E/e’. Results: LV ejection fraction was normal in both groups (HCM: 68 ± 7%; Controls: 65 ± 5%). Myocardial stiffness by iVP was markedly higher in HCM vs. controls (Fig.A, left panel). This was confirmed by EDPVRs, which were steeper and shifted leftward (Fig. B, left). The slope (β, load-independent) of EDPVR and CS (dP/dV) were higher and LV capacitance (V 30 , estimated volume at 30 mmHg EDP) was lower in HCM (Fig. B, right) and correlated significantly, though weakly, with iVP (β: r = 0.41; CS dP/dV: r = 0.48; EDP: r = 0.61; p<0.002 for all). Patients with apical variant had lower levels of global iVP compared to patients with predominant septal LVH and diffuse concentric LVH (Fig. A, right). Conclusions: Myocardial stiffness measured noninvasively by the intrinsic wave method is highly abnormal in HCM. This novel approach allows mapping of myocardial elasticity of the entire left ventricle and shows promise to become a clinical tool for evaluation of patients with diastolic tissue abnormalities.

Introduction: Loss-of-function (LOF) and gain-of-function (GOF) pathogenic variants in the KCNH2 -encoded Kv11.1 potassium channel cause type 2 long QT syndrome(LQT2) and type 1 short QT syndrome (SQT1), respectively. Given the prevalence of KCNH2- mediated heart disease (1 in 8000 for LQT2,1 in 100,000 for SQT1) and the reduced penetrance/variable expressivity seen in LQTS and SQTS, large databases such as the Genome Aggregation Database (gnomAD, n=141,352 individuals) might harbor subjects with unidentified LQT2/SQT1-causative mutations. Objective: To determine which “ultra-rare” KCNH2 missense variants (MVs) in gnomAD are most likely to be LQT2- or SQT1-causative. Methods: A list of gnomAD-derived MVs in KCNH2 was compiled. The frequency of each MV in gnomAD was assessed. Each MV was analyzed by 8 in silico pathogenicity prediction tools. MVs that were seen once in gnomAD and predicted damaging by all 8 tools were considered possible LQT2/SQT1-causative MVs worthy of functional validation via whole-cell patch clamp. Results: Overall, 233/474 (49%) of gnomAD KCNH2 MVs were seen in just 1 of >140,000 subjects. Of these, 2 (0.4%) MVs (S320W, S379Y) were predicted damaging by 8 in silico tools. Both S320W and S379Y localize to the N-terminus of the Kv11.1 potassium channel. There was no significant change in peak or tail current density between heterozygously expressed KCNH2-S320W (n=13, p=NS) and KCNH2-WT (n=13). However, heterozygous KCNH2-S379Y (n=12) produced a marked increase in peak current density across the range -30 mV to +20 mV and shifted the V 1/2 of activation by -17 mV (p < 0.001). Also, tail current density of S379Y channels significantly increased across the range -20 mV to +20 mV and the V 1/2 of deactivation shifted by -26 mV (p < 0.001). Conclusion: With this stringent requirement of ultra-rarity, universal prediction of damaging impact, and functionally abnormal electrophysiological properties, one SQT1-causative pathogenic variant in gnomAD was identified consistent with the predicted frequency of SQTS. The search continues among the remaining 32 ultra-rare MVs in KCNH2 where at least 75% of the in silico tools predicted deleterious impact of the MV to find the 15-20 subjects in gnomAD’s population who ought to have an LQT2-causative MV.

Background: The Metabolically Obese Normal Weight (MONW) phenotype has been described as a unique subgroup of individuals with metabolic dysregulation similar to obese individuals, but not considered obese per se . In theory, these individuals have an adiposity-independent substrate predisposing them to metabolic dysregulation. We tested whether central obesity explains the metabolic abnormalities in persons with MONW in a prospective population-based cohort in the Czech Republic. Methods: We used data from Kardiovize Brno 2030 study, a prospective community-based cohort in Central Europe. We defined obesity using World Health Organization categories for body mass index (BMI) and central obesity by waist circumference (WC≥ 94 cm in men and ≥ 80 cm in women). Metabolically obese (MO) was defined using AHA criteria by having three or more of the following: Hypertriglyceridemia (≥ 1.7 mmol/l); HDL cholesterol level <1.0 mmol/l in men or <1.3 mmol/l in women; elevated blood pressure (systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg) or antihypertensive drug treatment or history of hypertension; elevated fasting plasma glucose ≥ 5.6 mmol/l; or drug treatment and central obesity. Results: Of the 2,056 participants (46% men; mean age= 47.2 years, SD=11.2) included in the current analysis, 975 (47.4%) had normal weight and 696 (33.8%) were overweight. Prevalence of MO in the overall sample was 20.6% (n=424), 3.7% (n=36) among those with normal BMI and 9.9% (n=204) among overweight individuals. From the 36 subjects with MONW, 33 (91.6%) had central obesity by WC, while 201/204 (98.5%) with metabolically obese overweight, had central obesity by WC. Remarkably, in a subgroup of people with no metabolic obesity factors nobody had central obesity, see Figure . Conclusions: Metabolic dysregulation in people labeled as MONW can be explained by excessive visceral adiposity and not by an inherent predisposition, independent of adiposity.These findings underscore the importance of identifying central obesity in clinical practice even if BMI is below the obese criteria.

Introduction: Bioprosthetic valve thrombosis (BPVT) is a well-recognized cause of prosthetic dysfunction. Anticoagulation restores prosthetic valve gradients, but long term outcomes and complications from therapy are unknown. Objectives: To define the complications and long-term outcomes of anticoagulant therapy for BPVT. Methods: Retrospective matched cohort study of patients treated with warfarin for presumed BPVT at a single center from 1999 to 2016. Controls with normal bioprostheses by echocardiography were matched 2:1 for age at implantation, gender, prosthetic valve position, and type of prosthesis (porcine / pericardial). Results: A total of 83 presumed BPVT patients (40 aortic, 21 mitral, 18 tricuspid, and 4 pulmonary) and 166 controls were included. Age at BPVT diagnosis was 60±19 yrs (41±41 months post implantation); 45 (54%) were male. Transvalvular gradients returned to baseline in 63 (76%) of the patients, after 5±4 months of warfarin; 60 (72%) patients were maintained on warfarin indefinitely. Recurrent BPVT was seen in 13 (16%) patients, 33±31 months after initial therapy. When compared to controls, warfarin-treated BPVT patients had similar incidence of stroke [4(5%) vs 5 (3%), p=0.49], peripheral embolic events [4(5%) vs 10 (6%), p=0.78)], and death [12 (14%) vs 28 (17%), p= 0.72] (Figure, left panel), but more bleeding requiring transfusion [18 (22%) vs 3 (2%), p<0.0001]. Presumed BPVT patients more often required surgical or percutaneous valve re-replacement (Figure, center panel); this difference persisted even when comparing only patients with confirmed BPVT (those who responded to anticoagulant therapy) vs. their matched controls (Figure, right panel). Conclusion: Warfarin anticoagulation for presumed BPVT is successful in the majority of patients, without increase in stroke, peripheral embolism or death, but at the cost of excess bleeding. Recurrent BPVT occured in 16% of patients. Importantly, patients with BPVT required more often valve re-replacement. This finding suggests that anticoagulant therapy does not fully restore prosthetic valve durability, and that BPVT patients should be closely monitored.

Background: Peripheral artery disease (PAD) is a prevalent condition affecting one in four patients with end stage renal disease (ESRD). Intermittent pneumatic compression (IPC) has proven benefits in PAD. We are conducting a trial testing the utility of IPC in the ESRD population by assessing the improvement in quality of life (QOL), functional limitation and walking performance from PAD-related symptoms. We aim to present our pilot results. Methods: Prospective single cohort study undergoing recruitment of outpatients at the hemodialysis (HD) unit of John H. Stroger Hospital. The calculated sample size is 78. PAD is confirmed by ankle-brachial index (ABI) and demographics obtained from interview and chart review. At baseline and post intervention, a Six-minute Walk Test (6MWT), Peripheral Artery Questionnaire (PAQ) and Walking Impairment Questionnaire (WIQ) are administered. The IPC device (Bio Arterial Plus) is used for intervention during HD. We present continuous variables as median (IQR) and categorical variables as percentage. Wilcoxon signed rank test was performed for comparison of results. Results: So far, 9 patients have completed intervention for the pilot study, 44% are men, the majority hispanic (66%), with age 48 (41-63) years. At baseline 66% of ABI were abnormal, all due to non-compressible PAD 1.46 (1.20-1.62). All patients have HTN, 44% diabetes, 33% hyperlipidemia and 33% heart failure. The median time of intervention is 70 (60-83) days. There was a significant difference in QOL measured by the WIQ (Fig.1), PAQ physical limitation (p=0.011), and PAQ social limitation (p=0.018). Although there was a trend towards benefit, no statistical difference was found on rest of objective and subjective measured parameters (p>0.05) Conclusions: Preliminary, IPC shows to improve many subsets of QOL in patients with ESRD and PAD. Given the small sample, improvement of walking distance remains elusive but with trends towards benefit.

Introduction: The incidence and etiologies underlying sudden cardiac arrest (SCA) in the young are derived from population- and referral-based cohorts of young SCA survivors. The extent to which the use of these cohorts contributes to discrepancies in our understanding of SCA in the young is unknown. As such, we sought to determine and compare the spectrum of SCA etiologies observed in young SCA survivors evaluated at a single tertiary center on both a primary and referral basis. Methods: Retrospective review of 940 young SCA survivors evaluated between 1990 and 2017 was used to identify all individuals ≤ 50 years of age that experienced a SCA. SCA root cause was determined by review of the medical records and diagnoses classified as ischemic, primary electrical, structural, or unexplained. SCA survivors that initially presented to our institution were classified as primary, while those who presented for secondary evaluation received a referral classification. Results: Overall, 566 SCA survivors were identified (age at event 33 ± 14 years; 39% females). In comparison to primary SCA survivors, referral SCA survivors were younger at the time of SCA (39 ± 12 vs. 30 ± 14 years; p<0.0001) and less likely to experience pre-SCA symptoms (45% vs. 27%; p<0.0001). Among all SCA survivors, the most common etiologies were idiopathic ventricular fibrillation (27%), acute coronary syndrome (21%), long QT syndrome (10%), and hypertrophic (7%) and dilated (6%) cardiomyopathies. Ischemic etiologies were less common (45% vs. 25%; p<0.0001) and primary electrical disorders more common (6% vs. 23%; p<0.0001) in referral SCA survivors. Conversely, genetic heart diseases (hypertrophic cardiomyopathy, long QT syndrome, etc.) were over-represented in referral cases (8% vs. 29%; p<0.0001), whereas no difference was observed in the number of primary and referral SCAs that remained unexplained. Conclusion: This study demonstrates, for the first time, that differences in SCA root cause exist between young SCA survivors evaluated at the same tertiary medical center on a primary vs. referral basis. Ongoing comparison of SCA etiologies between primary and referral SCA survivors may help resolve discrepancies regarding the contribution of specific disorders to SCA in the young.

Introduction: Baseline hemodynamic parameters have been shown to predict postoperative outcomes such as right ventricular failure (RVF) in LVAD patients. The pressure adjusted heart rate (PaHR) is a hemodynamic parameter that has not been reported in LVAD recipients. Hypothesis: Patients with an elevated PaHR at baseline will have an increased risk of adverse outcomes following LVAD implantation. Methods: Historical cohort study of 273 patients with preoperative invasive hemodynamic assessment before durable LVAD implantation from January 1 st , 2007 to April 10 th 2017. Baseline patient characteristics and hemodynamic parameters were assessed. The primary endpoint was a composite of 30 day mortality, stage 3 acute kidney injury (AKI), and postoperative RVF. Univariate analysis was used to identify predictors of the composite endpoint, which were entered into stepwise backwards multivariate logistic regression to determine independent predictors of the composite outcome. Results: The mean age was 59 and 79% of the patients were male. The median INTERMACS profile was 4 and 166 (60%) of LVADs placed were as destination therapy. The primary composite endpoint was reached by 74 (27%) patient, including 30-day mortality in 13 (5%), severe AKI in 48 (18%) and RVF in 53 (19%). Univariate predictors of the composite endpoint (p <0.05) included atrial fibrillation, INTERMACS profile, home inotropes, preoperative IABP, admission creatinine, baseline Vasoactive-Inotropic Score, mean right atrial pressure (mRAP), mRAP/wedge, mean arterial pressure/mRAP, mean pulmonary artery pressure/mRAP, right ventricular stroke work index (RVSWi), pulmonary artery pulsatility index, and the PaHR. Logistic regression identified PaHR (OR 0.96, 95% CI 0.93-0.99, p=.026), RVSWi (OR 1.002, 95% CI 1.001-1.004, p=.002), home inotropes (OR 0.46, 95% CI 0.22-0.94, p=.034), atrial fibrillation (OR 0.48, 95% CI 0.26-0.88, p=.019) and admission creatinine (OR 0.51, 95% CI 0.34-0.77, p=0.002) as predictors of the composite endpoint. Conclusions: The PaHR is a readily available, novel hemodynamic parameter, that when elevated on baseline hemodynamic assessment can predict those patients at increased risk of postoperative adverse outcomes after durable LVAD implantation.

Introduction: Patients at increased risk of complications following LVAD placement are admitted to the hospital for hemodynamic optimization prior to LVAD implantation, which can include adjustment of medical therapy and/or placement of an IABP. Hypothesis: Prior to LVAD placement patients treated with an IABP during hemodynamic optimization will have similar outcomes despite worse baseline characteristics compared with patients treated medically. Methods: This single-center study included 199 non-inotrope dependent patients who underwent durable LVAD implantation between January 1 st , 2007 and April 10 th 2017. Hemodynamic data was collected retrospectively. Patients who received an IABP were compared to those who did not. Stage 2 or 3 acute kidney injury, right ventricular failure, and 30 day mortality was compared between patients with and without and IABP. Results: The mean age was 62.7 and 82.9% were male; 72 (36.2%) received an IABP. Baseline characteristics between groups were similar. Patients treated with an IABP had worse INTERMACS profiles and worse baseline hemodynamic parameters. The incidence of the primary composite endpoint was similar between patients who had an IABP and those who did not (23.6% vs 19.7%; p=0.517), as were each of the individual endpoints: stage 2 or 3 acute kidney injury (18.1% vs 14.2%; p=0.472), right ventricular failure (13.9% vs 13.4%; p=0.796), and 30 day mortality (6.9 % vs 3.2%; p=0.226). Patients treated with an IABP had greater relative reductions in mean right atrial pressure (-24.1% vs -5.9%; p=0.044), pulmonary artery systolic (-11.7% vs +3.3%; p=<0.001), diastolic (-17.0% vs +12.0%; p=0.015), and mean pressures (-15.2% vs 0.5%; p=<0.001). Conclusions: Despite worse hemodynamic parameters and INTERMACS profile at baseline, ambulatory heart failure patients who received an IABP prior to LVAD implantation did not have an increased incident of stage 2 or 3 acute kidney injury, right ventricular failure, or 30 day mortality, and had more favorable reductions in right atrial and pulmonary artery pressures. These results suggest that the use of the IABP prior to LVAD implantation in non-inotrope dependent patients with poor baseline hemodynamics may mitigate the risk of postoperative complications.

Introduction: Studies have demonstrated an association between hyperkalemia and increased mortality in patients with myocardial infarction, but limited data exist regarding hyperkalemia and associated death among unselected cardiac intensive care unit (CICU) patients. Hypothesis: Hyperkalemia is associated with mortality in CICU patients. Methods: Historical cohort of 9,681 CICU patients admitted from January 2007 to December 2015 with serum potassium measured on admission. Hyperkalemia was defined as admission potassium >=5.0 mEq/L, normokalemia as admission potassium 3.5-4.9 mEq/L, and hypokalemia as admission potassium <3.5 mEq/L. Multivariate logistic regression was used to determine predictors of hospital mortality. Post-discharge survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models. Results: Mean age was 67±15 years with 3,629 (36%) females and hospital mortality of 9%. Hyperkalemia occurred in 1,187 (12.3%), and hypokalemia occurred in 719 (7.4%). Compared to normokalemic patients, both hyperkalemic patients (unadjusted OR 2.85, 95% CI 2.40-3.39; P<.001) and hypokalemic patients (unadjusted OR 2.31, 95% CI 1.85-2.88; P<.001) were at increased risk of hospital mortality. After adjustment for illness severity and renal function, only hyperkalemic patients were at increased risk of hospital death (adjusted OR 1.35, 95% CI 1.07-1.69; p = 0.01), while hypokalemic patients were not (P = NS). Among hospital survivors, hyperkalemic patients had lower post-discharge survival by Kaplan-Meier analysis (P <0.001), while hypokalemic patients had similar survival compared to normokalemic patients (p = NS). After adjustment for illness severity and renal function, hospital survivors with hyperkalemia were at increased risk for post-discharge mortality compared with normokalemic patients (adjusted HR 1.16, 95% CI 1.05-1.28; p=.003). Conclusions: Hyperkalemia on CICU admission is associated with higher hospital and post-discharge mortality, independent of renal function and illness severity. This emphasizes the importance of potassium abnormalities as a risk predictor in patients admitted to the CICU.