Citations

Backgrounds: Role of coronary artery calcium score (CACS) in acute chest pain patients is currently not well defined. The objective of this study was to investigate the prognostic value of CACS obtained by noncontrast electrocardiogram-gated CT in acute chest pain patients suspected for cardiac origin in emergency department. Methods: We search Pubmed, Embase, Cochrane databases for longitudinal studies of CACS in acute chest pain patients without known coronary artery disease (CAD) in emergency department which reported major adverse cardiovascular events (MACE), consisting of death, nonfatal myocardial infarction (NFMI), revascularization or stroke. Pooled annualized event rate, risk ratios and 95% confidence intervals (CI) were analyzed. A random-effect, generic inverse variance model was used. Result: Eight studies evaluated 3556 patients (mean age = 51 years, 47% men) with the pooled prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking of 42%, 16%, 33% and 33% respectively. During a median follow-up of 5 months (range 1-60 months, 37234 patient-months), the overall pooled MACE rate was 7.6%/y. The pooled event rate of MACE for CACS=0 versus CACS>0 was 0.8%/y (13 events in 18874 patient-months) versus 14.6%/y (224 events in 18360 patient-months). The pooled risk ratio with CACS=0 was 0.04 (95% CI: 0.02-0.07, p<0.001) for MACE compared to CACS>0. The sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio of CACS for MACE was 94.5%, 64.1%, 15.8%, 99.4%, 2.63 and 0.09 respectively. The heterogeneity among studies was low with an I 2 of 13%. Conclusion: In acute-chest-pain patients without known CAD presenting to emergency department, MACE was rare in those with CACS=0. Zero CACS by noncontrast electrocardiogram-gated CT in this population has high negative predictive value (>99%) for subsequent cardiac events.

Objective: To evaluate outcomes of endovascular treatment of aortic coarctation in the adult, either newly diagnosed or due to recurrent coarctation and pseudoaneurysm formation Methods: Clinical data and imaging studies of 93 patients treated at nine institutions from 1999-2015 were reviewed. Primary end-points were morbidity and mortality. Secondary end-points were stent patency and need for re-intervention Results: There were 54 male and 39 female patients with a mean age of 44±17 years, including 32 with de novo coarctation (mean 48±16 years) and 61 with prior open repair during childhood, who required endovascular re-intervention (mean: 30±17 years after initial repair). Indications for treatment were: resistant hypertension (32%), left ventricular hypertrophy (23%) and claudication (20%). Imaging studies included: computed tomography angiography (CTA) (42%), CTA and magnetic resonance angiography (MRA) (37%), MRA (13%), angiography (5%) and ultrasound (2%). Endovascular treatment was performed using stent grafts (55%), balloon expandable bare metal in (28%) or covered stents (15%) and primary angioplasty alone (1%). Mean lesion length and diameter were 64±50mm and 20±7mm, respectively. Mean systolic pressure gradient decreased from 24±18mmHg to 5±8mmHg after treatment, (p<0.001). Four patients had intraprocedural complications including: rupture in two, type 1A endoleak and access hemorrhage in one each. Perioperative complications occurred in six: aortic dissection in three, thrombus migration into renal artery, spinal headache requiring blood patch and lung hemorrhage in one patient each. Two patients died within 30-days from hemorrhage and cardiopulmonary arrest. After a mean follow up time of 7±21 years, nearly all patients (98%) had symptom improvement and all stents were patent. Re-intervention was needed in 11%. 2 patients died from coarctation related causes including rupture of an infected graft and visceral ischemia Conclusions: In this multi-center study, endovascular repair was a safe and effective treatment for de novo coarctation and post-surgical complications of coarctation repair in adults. Rate of procedural complications and re-interventions were low with high procedural and long-term clinical success

Objectives: CABG and PCI are used for revascularization of multivessel coronary artery disease (MVCAD). However, limited information is available comparing the rates of in-hospital and 30-day major adverse cardiac and cerebrovascular event (early MACCE), including early death, stroke, myocardial infarction (MI), and repeat revascularization, among patients with multiple arterial CABG (MultArt) vs PCI. Methods: We reviewed 12,615 MVCAD patients with isolated primary CABG or PCI from 1993 through 2009. CABG patients (n=6,667) were grouped by number of arterial grafts into left internal mammary artery/saphenous vein (LIMA/SV) (n=5,712) or MultArt (n=955); PCI patients (n=5,948) into balloon angioplasty (BA) (n=1,020), bare metal stent (BMS) (n=3,242), and drug-eluting stent (DES) (n=1,686). Results: Early MACCE rate was significantly greater for PCI than CABG (8.5% vs 4.1% [P<.001]) and lower for MultArt than LIMA/SV or PCI (1.5% vs 4.5% and 8.5%, respectively [P<.001]). Stroke and early death rates were higher in CABG vs PCI (2.2% vs 0.4% [P<.001], and 1.5% vs 1.0% [P=0.01], respectively), whereas MI and repeat revascularization were lower (0.5% vs 6.0% and 0.3% vs 2.2%, respectively [P<.001]). Stroke and early death were similar in MultArt and PCI and lower vs LIMA/SV (0.6% and 0.4% vs 2.6%, and 0.5% and 1.0% vs 1.7%, respectively [P<.001]); MI and repeat revascularization rates were similar in MultArt and LIMA/SV and lower vs PCI (0.4% and 0.6% vs 6.0%, and 0.3% and 0.3% vs 2.3%, respectively [P<.001]). In propensity score-matched analysis, CABG had significantly improved early MACCE rate compared with BA (4.7% vs 13.2% [P<.001]), BMS (4.3% vs 8.3% [P<.001]), and DES (2.9% vs 5.5% [P=.008]), and MultArt compared with PCI (1.8% vs 7.8% [P<.001]) fig. Conclusions: In MVCAD patients undergoing isolated primary revascularization, CABG conferred lower early MACCE rate vs PCI. Early MACCE rate was markedly decreased after MultArt compared with LIMA/SV, BA, BMS, and DES.

Background: There is sparse comparative data on short-term readmissions following Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Methods: The study cohort was derived from the National Readmission Data (NRD) 2013, a subset of the Healthcare Cost and Utilization Project (HCUP) sponsored by AHRQ. TAVR and SAVR were identified using appropriate ICD-9-CM codes (TAVR - 35.05, 35.06 & SAVR - 35.21, 35.22) as either primary or secondary procedural codes. Variables which could affect treatment assignment, were adjusted with propensity score match analysis and Match (1:1) cohort was generated. Readmission causes were identified by ICD 9 code in primary diagnosis. Results: Our analysis included 3,886 TAVR and SAVR procedures each in the propensity matched cohorts. There was no significant difference in terms of readmission rates amongst patients who underwent TAVR vs. SAVR [21.41% vs. 21.07% (OR: 1.02, 95% CI: 0.92 - 1.14) p = 0.702]. Cardiac etiologies were more likely to be responsible for readmissions following SAVR (42.66% vs. 35.91%, p = 0.006). Atrial fibrillation (AF) was a much more common cause of readmission following SAVR (7.81% vs. 3.37%, p <0.001). Overall vascular (3.24% vs. 1.32%, p = 0.006) and bleeding complications (9% vs. 6.2%, p = 0.025) were more likely to result in readmission in patients undergoing TAVR. Cost of care of index admission and readmission was similar in both groups. Readmission mortality was higher amongst patient with TAVR vs. SAVR (6.49 vs. 3.91, p = 0.02). 50% of TAVR and SAVR readmission occur within 11 days post discharge. Conclusion: In our study from a large nationwide database, there was no significant difference in readmission rate, median readmission rate and resource utilization between TAVR and SAVR. Arrhythmias especially AF accounted for more SAVR readmission and Bleeding/vascular complications were more commonly responsible for readmissions following TAVR.

Introduction: We compared outcome of repeat CABG (RCABG) and PCI in patients with previous CABG. Hypothesis: RCABG may improve survival versus PCI. Methods: From 1993 through 2009, 3,058 patients underwent revascularization after previous CABG. RCABG patients (n=530) were grouped by the use of arterial grafts (n=396), or saphenous vein grafts (SVG; n=134). At previous CABG, 37% of RCABG patients received IMA graft. PCI patients (n=2,528) were grouped into balloon angioplasty (BA; n=491), bare metal stent (BMS; n=1,267), and drug-eluting stent (DES; n=769). PCI patients were further stratified by the treated target into native coronary artery (n=1,637), bypass grafts (n=674), or both (n=216). Propensity score analysis matched 287 patients. Results: RCABG had increased 30-day mortality compared with PCI (HR=3.92; 95% CI, 2.25-6.84; P <.001) in multivariable analysis, while in propensity matched analysis it did not ( P =.09). Overall survival, however, was greater for RCABG compared with PCI in multivariable analysis (HR=0.70; 95% CI, 0.59-0.83; P <.001), as well as in propensity matched analysis (10-year survival rates were 52% vs 37%, respectively [ P =.005]). Compared with RCABG, PCI involving bypass grafts had increased mortality (HR, 1.39; 95% CI, 1.09-1.78; P =.008), whereas PCI targeting only the native coronaries did not (HR, 1.12; 95% CI, 0.85-1.47; P =.43); BMS patients had increased mortality (HR, 1.34; 95% CI, 1.06-1.68; P =.013), but DES did not (HR, 1.28; 95% CI, 0.77-2.12; P =.35). At RCABG, 318 patients (60%) received an IMA graft and late survival was similar to those receiving SVG; The use of IMA in previous CABG was associated with improved survival (HR=0.82; 95% CI, 0.72-0.92; P <.001]. Conclusions: Long-term survival after previous CABG is improved with RCABG compared to PCI, especially when PCI involves bypass grafts. There is no difference in long-term survival between RCABG using arterial grafts vs SVG only if IMA is used in either previous or RCABG.

Background: Bystander CPR (BCPR) and telephone CPR (TCPR) are associated with improved OHCA outcomes. It has been shown that BCPR increases the proportion of patients with an initial shockable cardiac rhythm (VF/VT) when encountered by EMS. It is unknown whether TCPR does the same. Objective: To assess whether TCPR is independently associated with an increase in initial shockable cardiac rhythms during OHCA. Methods: Data from 9-1-1 audio recordings, first care EMS reports and hospital records were linked for OHCAs of presumed cardiac origin (1/2011-12/2014). Three cohorts were analyzed: TCPR, BCPR or no CPR. Using no CPR as the reference group, we assessed whether TCPR and BCPR were independently associated with initial shockable rhythms in a logistic regression model controlling for gender, event location, witness status and EMS response interval. Results: After exclusions, 2715 adult OHCA events with linked outcome data were analyzed (median age: 63; male: 66.8%; 33.3% witnessed arrest). Median response interval was 5 min. The BCPR rate (lay rescuer CPR without telephone instructions) was 24.8% and survival in this group was 15.4%. The TCPR rate (lay rescuer CPR with telephone instructions) was 40.2% and survival in this group was 11.7%. For the no-CPR group, 20.5% had an initial shockable rhythm. For the BCPR group, 34.6 % had an initial shockable rhythm. For the TCPR group, 23.2% had an initial shockable rhythm. Provision of BCPR and of TCPR were each independently associated with shockable rhythms [aOR (BCPR) = 1.7, 95% CI: 1.33-2.17, p=0.0001; aOR (TCPR) = 1.3, 95% CI: 1.04-1.63, p=0.0001]. Conclusion: The provision of both BCPR and TCPR were independently associated with an increased rate of initial shockable cardiac rhythms and an increase in survival to hospital discharge compared to no CPR.

Introduction: Isolated cases of liver injury associated with the use of non-vitamin K antagonist oral anticoagulants (NOACs) have been reported. However, the comparative incidence of liver injury in users of different oral anticoagulants is unknown. Methods: We studied 113,717 patients (mean age 70, 39% women) with non-valvular atrial fibrillation (AF) included in the MarketScan® Commercial and Medicare Supplemental databases with a first prescription for oral anticoagulation after November 4, 2011, followed through December 31, 2014. Of these, 56,879 initiated warfarin, 17,286 initiated dabigatran, 30,347 initiated rivaroxaban, and 9,205 initiated apixaban. Liver injury hospitalizations were identified using selected inpatient diagnostic codes. Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of liver injury by anticoagulant type. Results: During a median follow-up of 12 months, 960 hospitalizations with liver injury were identified. Rates of liver injury hospitalization (per 1000 person-years) by oral anticoagulant were 9.0 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban), and 5.6 (apixaban). After multivariable adjustment, rates of liver injury hospitalization were lower in initiators of NOACs compared to warfarin: HR (95%CI) of 0.57 (0.46, 0.71), 0.88 (0.75, 1.03) and 0.70 (0.50, 0.97) for initiators of dabigatran, rivaroxaban, and apixaban, respectively (Table). Compared to dabigatran initiators, rivaroxaban initiators had a 56% increased risk of liver injury hospitalization (HR 1.56, 95%CI 1.22, 1.99). In addition to type of anticoagulant, prior liver, gallbladder, and kidney disease, cancer, anemia, heart failure, and alcoholism significantly predicted liver injury hospitalization. Conclusions: Among patients with non-valvular AF, NOACs were associated with lower risk of liver injury hospitalization compared to warfarin, with dabigatran showing the lowest risk.

Introduction: Coronary angiography (CA) is recommended after out-of-hospital cardiac arrest (OHCA) when ST-elevation is present but the ideal timing and benefit of CA when ST-elevation is not present are unknown. Methods: Prospective observational study of adult (age >17) OHCA of presumed cardiac etiology from 1/01/2010-12/31/2014 who were admitted to one of 40 recognized cardiac receiving centers within a state resuscitation center network. DNR patients, those who did not achieve ROSC, and/or those who died in the ED were excluded since the likelihood of percutaneous coronary intervention (PCI) impacting outcome in these patients is low. An in-hospital database was linked with a statewide OHCA database. Results: Among 6,615 cases, 1,247 remained for analysis after exclusion [DNR (1254); failed to achieve ROSC/died in ED (4,020); missing prehospital variable (92); and missing outcome (2)]. Median age was 63 and 70% were male. There were 62% witnessed arrests, 54% received bystander CPR and the initial rhythm was VF/VT in 55%. Sixty-four percent survived to hospital discharge, 82% of which had a CPC score of 1 or 2. Of the 326 STEMI cases, 298 (91%) underwent CA with resultant PCI in 206 (63%). Of the 849 non-STEMI cases, 361 (43%) underwent CA with resultant PCI in 107 (13%). Overall survival was: 54% in cases without CA; 73% in cases with CA but without PCI; and 73% in those with PCI. Survival in non-STEMI cases was: 55% in cases without CA; 82% in cases with CA but without PCI; and 80% in those with PCI. In non-STEMI cases, the adjusted odds of survival for CA without PCI vs no CA was 2.70 (95% CI: 1.81, 4.02) and for PCI versus no CA it was 2.01 (95% CI: 1.16, 3.48). Conclusion: In this statewide analysis over 90% of OHCA cases with STEMI underwent CA. In cases that were not STEMI, CA was strongly and independently associated with survival regardless of whether PCI was performed. Since there is no reason to believe that CA without PCI confers a survival benefit, these findings suggest a component of selection bias in those without STEMI who undergo CA.

Introduction: While left ventricular assist devise (LVAD) support improves the prognosis of end-stage heart failure (HF) patients, the long-term outcomes remains suboptimal. Improved outcomes may occur with organ protection including reverse myocardial remodeling. Cenderitide (CDNP) is a Mayo engineered designer natriuretic peptide (NP) that co-activates particulate guanylyl cyclase A and B receptors and functions via the second messenger cGMP. We reported a NP deficient state in the heart with LVAD support which lays the rationale for NP replacement therapy with Cenderitide which has cardiorenal protective actions in experimental HF. We sought to determine if Cenderitide co-therapy would be safe and activate cGMP in patients with LVAD support. Hypothesis: Acute single dose of subcutaneous (SQ) Cenderitide will be safe and activate cGMP in patients with LVAD support. Methods: Stable HF patients with LVAD support (Heartmate II, all males) were enrolled in a cross-over design comparing SQ placebo and low (Low-C, 5 ug/kg, n=8) or high dose (High-C, 10 ug/kg, n=8) Cenderitide (Capricor Therapeutics) administration. Vital signs, plasma C(D)NP, cGMP, Aldosterone (Aldo), and NT-proBNP levels were measured before or after drug administration over 24 hours. All parameters in Cenderitide group were adjusted by those in placebo. Results: Both Low-C and High-C group demonstrated significantly increased plasma C(D)NP and cGMP levels for 2 hours after drug injection and those in High-C group showed more prolonged and higher increases than Low-C group. Mean arterial pressure (MAP) in Low-C did not show any changes but in High-C group tended to be lower for 18 hours but this was not significant. Plasma Aldo and NT-proBNP levels in Low-C group did not show any change but those in High-C group tended to be lower after drug injection s similar to the change in MAP. No adverse events were observed in the study. Conclusions: SQ Cenderitide was successfully absorbed, activated cGMP and well tolerated in patients with LVAD support. High dose Cenderitide may have cardiac unloading effects suggested by decreases in NT-proBNP. Further clinical trial for efficacy is warranted to clarify cardiorenal protective effects of Cenderitide in the LVAD population to improve outcomes.

Background: Troponin-T (TnT) elevation is common in severe sepsis and septic shock, but the impact on mortality and other clinical outcomes remains uncertain. Methods: This was a retrospective review of adult patients with severe sepsis and septic shock admitted to all the intensive care units (ICU) at Mayo Clinic, Rochester from January 2012 to December 2014. Patients with congenital heart disease or pre-existing moderate or greater valvular disease were excluded. TnT elevation was defined as initial TnT ≥0.1 ng/mL or rise in 3- and 6-hour TnT ≥0.03 ng/mL. Primary outcomes included ICU, hospital, 28-day and 1-year mortality and secondary outcomes were need for and duration of non-invasive ventilation or invasive mechanical ventilation, ICU readmission, and ICU and hospital length of stay. Two-tailed p <0.05 was considered statistically significant. Results: During this three-year period, TnT was measured in 372/765 patients (49%) with septic shock with TnT elevation noted in 329/372 (88%) patients. In patients with and without TnT elevation, initial TnT was 0.14±0.26 vs. 0.14±0.02 ng/mL, p =0.57 and peak TnT was 0.20±0.36 vs. 0.08±0.11 ng/mL, p <0.001. Severity of illness scores, laboratory values, vasopressor use, clinical parameters and medications were similar between patients with and without TnT elevation, except that patients with TnT elevation were older and had more frequent history of coronary atherosclerosis, chronic kidney disease, heart failure and atrial fibrillation (all p <0.05). There was no significant difference in ICU mortality [43 (13%) vs. 8 (19%), p =0.34] and hospital mortality [75 (23%) vs. 12 (28%), p =0.45] between patients with and without TnT elevation. Long-term follow-up of 220/329 (67%) patients showed no significant difference in 28-day mortality [97/216 (45%) vs. 1/4 (25%); p =0.63] or 1-year mortality [163/216 (75%) vs. 4/4 (100%); p =0.58]. There was no significant difference in any of the secondary outcomes between patients with and without elevated TnT (all p >0.05). There was no difference in mortality with increasing quartiles of peak TnT. Conclusions: Troponin elevation is associated with older age and higher comorbidity burden, but does not predict mortality in patients with severe sepsis and septic shock.