bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4353: Economic Burden of Prolonged Hyponatremia in Patients Admitted with Congestive Hear Failure (CHF) and Hyponatremia
Authors: Tabak Ying P , Zilberberg Marya , Spalding James , Sun Xiaowu , Liu Yan , Gupta Vikas , Shorr Andrew F
Published: July 2021

Introduction
: Hyponatremia is a common electrolyte abnormality present in patients hospitalized with CHF.

Hypothesis
: We sought to evaluate that the rate of correction of hyponatremia impacts the length of stay (LOS) and associated hospitalization cost.

Methods
: We analyzed 9,427 hyponatremic (Na<135 mEq/L) CHF patients hospitalized in 2003–2006 across 72 hospitals. Based on evaluation of hospital survival, we found a lower mortality with a Na rate of rise in the first 48 hours of 1– 6 mEq/L (favorable group). We conducted multivariable regression to estimate the effect of Na management on LOS and cost, controlling for baseline Na, admission severity, mortality status, and interaction of severity and mortality. Hospitalization cost was calculated by hospital and calendar year using the Center for Medicare and Medicaid Services (CMS) cost/charge ratios.

Findings
: The overall in-hospital mortality was 5.7%. The rate of favorable Na management within 48 hours of hospitalization was 60% (n=5,647). About 38% (n=3,557) patients had hyponatremia status unchanged or further deteriorated from baseline (prolonged hyponatremia). Another 2% (n=218) had Na corrected more than 7.0 mEq/L. After adjusting for confounders, the prolonged hyponatremia group showed 0.71 day increase in the LOS (95% CI: 0.45, 0.97 days; p<.0001) and $1,324 excess cost (95% CI: $569, $2,079; p<.001). The overcorrection group did not show significant difference in LOS and cost from the favorable Na group.

Conclusions
: Only 60% CHF patients with admission hyponatremia are managed favorably in regards to the rate of serum Na correction. The adjusted mean marginal excess LOS of prolonged hyponatremia is about 1 day and the excess cost is over $1,300. Recognition and institution of measures to insure an appropriate and predictable rate of Na correction are needed in order to improve economic outcomes among hyponatremic patients with CHF.
Abstract 4378: Apoptosis in Heart Failure Predominantly Involves Non-Myocytes
Authors: Park Misun , Shen You-Tang , Fritzky Luke F , Tian Bin , Depre Christophe , Yan Lin , Gaussin Vinciane , Kitsis Richard N , Vatner Dorothy E , Vatner Stephen F
Published: July 2021

Apoptosis has been considered a cardinal sign of heart failure (HF) and a major factor in its pathogenesis. If the loss of myocytes contributes to the development of HF, it is assumed that the apoptosis occurs in cardiomyocytes, which reside in otherwise viable tissue in myocardium adjacent and remote to the infarct. We tested this hypothesis in a non-human primate model of chronic HF induced by rapid pacing, 2–3 months following myocardial infarction (MI). Left ventricular (LV) ejection fraction decreased in MI (from 75±6.2 to 56±5.2%, p<0.05) and further, p<0.05, in HF (27.8±2.8%). Apoptosis was assessed by TUNEL and by caspase-3 cleavage. As expected, apoptosis increased in MI, p<0.05, and further, p<0.05, when HF developed, and was greater in adjacent than remote myocardium (Table 1

). In order to discriminate apoptosis in non-myocytes and myocytes, the myocardium was stained with cleaved caspase-3, and counterstained with rhodamine-conjugated wheat germ agglutinin (WGA) or with troponin-I, a cardiac muscle marker. The ventricular myocytes were stained by WGA at the outer membrane and across in a striated pattern as associated with the T tubule network. Surprisingly, the majority of apoptotic cells in MI and MI+HF and in both adjacent and remote areas were non-myocytes (Table 1

). For characterization of types of non-myocytes, serial tissue sections were immunostained with antibodies recognizing macrophages (HAM56), neutrophils (elastase NP57), and endothelial cells (CD31). Macrophages were the cell type contributing the largest fraction of apoptotic non-myocytes (47%). In conclusion, HF does induce apoptosis in the heart, but it occurs predominantly in non-myocytes, suggesting that the role of apoptosis in the pathogenesis of HF may not simply be due to simple loss of myocyte contractile elements.

Table 1
Abstract 4386: Single-Center Experience in Large Cohort of Patients with Pulmonary Arterial Hypertension Related to Congenital Heart Disease over 15 years: Effect of New Therapies
Authors: Apostolopoulou Sotiria C , Tsoutsinos Alexandros , Kiaffas Maria , Laskari Cleo V , Rammos Spyridon
Published: July 2021

Introduction: The aim of this study was to define the epidemiology, clinical parameters and 15-year follow-up of a large single-center cohort of patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD) and to evaluate the effect of emerging therapeutic strategies in this population.

Methods: All patients diagnosed with PAH related to CHD between 1993 and 2008 were studied and clinical, echocardiographic, maximal and submaximal exercise as well as hemodynamic data were recorded.

Results: A total of 60 pts aged 21 ± 14 (0.1–51) years at diagnosis were included in the study. Of these, 44 (73%) had unrestrictive mixing lesions and Eisenmenger syndrome and the rest non-mixing lesions, mainly repaired CHD. Of this population, 24 (40%) were <18yrs and the remainder adults at diagnosis at our institution. Seven (12%) pts in WHO Class II received no therapy, 45 (75%) pts in Class II-III monotherapy (34 bosentan with 1 discontinuation after corrective surgery, 6 sildenafil, 5 sitaxsentan) with clinical and exercise improvement. Due to deterioration, 6 (10%) pts received addition of sildenafil after 3±1 years of bosentan monotherapy and 2 (3%) pts addition of epoprostenol after 1 year of the above combination therapy. Over 6±4 (1–15) years of follow-up, 49 (82%) pts remained stable on no or monotherapy, 4 pts (7%) deteriorated after 1–5 years monotherapy but stabilized on combination therapy and 7 (12%) pts died (3 from intractable right heart failure despite escalation of therapy and 4 suddenly while on therapy). The unrestrictive mixing group had 2 (4%) and the non-mixing group 5 (33%) deaths respectively.

Conclusions: Long-term improvement and stabilization is possible in pts with PAH related to CHD with either monotherapy or combination therapy in case of deterioration overtime while on treatment. Death in this population may be sudden or due to intractable right heart failure, while survival is significantly better in pts with unrestrictive mixing. Larger long-term registry studies are needed to evaluate survival and clinical condition of these pts in the current treatment era and to improve medical management of this population.
Abstract 4388: In-Vivo Pulmonary Vascular Stiffness Obtained from Color M-Mode Tissue Doppler Imaging and Pressure Measurements Predicts Clinical Outcomes Better than Indexed Pulmonary Vascular Resistance in Pediatric Patients with Pulmonary Arterial Hypertension
Authors: Hunter Kendall S , Lanning Craig J , Kirby K Scott , Ivy D Dunbar , Shandas Robin
Published: July 2021

Introduction: Pulmonary vascular stiffness (PVS) is increasingly recognized as an important component of right ventricular afterload in patients with pulmonary arterial hypertension (PAH). In adult and pediatric PAH populations, stiffness has also been shown to improve prediction of mortality and outcomes, respectively. Despite these promising findings, methods to determine PVS clinically remain limited. Here we examine the ability of a minimally-invasive method to quantify proximal PVS in a pediatric PAH population, and hypothesize this measurement will offer better disease outcomes prediction over indexed pulmonary vascular resistance (PVRI), the current gold standard.

Methods: Color M-mode Tissue Doppler Images of the right pulmonary artery (RPA) were obtained using ultrasound during right-heart catheterization of 36 individuals undergoing reactivity testing (n=86) who ranged in age from 1 month to 19 yrs (mean = 6.5±5.2 yrs, 19 males). These measurements yielded RPA diameter and intravascular pressure, from which an estimate of the circumferential elastic (Young’s) modulus (E), the continuum component of stiffness, was derived. Echo imaging added only 5 minutes to the procedure. Follow up was obtained in 19 patients (mean = 4.9±4.7 yrs, range 1 month to 16 yrs, 9 males) at a median time of 15 months (range 1–26 months). Cumulative logistic regression was used to relate continuous values of E and PVRI to three outcomes categories: improvement; stable (no change); or worsening. These were determined from change in WHO score from initial assessment to follow up.

Results: E had better correlation to pulse pressure (PP) (R2=0.61) compared to mean pressure (R2=0.43); this agrees with other findings of PP as a good proxy of stiffness. E displayed substantially better correlation (R2L=0.49) to outcomes compared to PVRI (R2L=0.33). In more practical terms, E wrongly predicted outcome only once (5%), compared to four errors by PVRI (21%), and offered clearer prognosis in an additional 3 individuals; thus 37% of the group would benefit from such improved prediction.

Conclusion: We conclude that elastic modulus is a measure of proximal vascular stiffening and most importantly offers superior outcomes prediction compared to pulmonary vascular resistance.
Abstract 4401: Two Independent Genetic Variants in NOS1AP are Associated with QT interval in a Multi-Ethnic Population: the Dallas Heart Study
Authors: Arking Dan E , Khera Amit , Xing Chao , Kao Wen H , Chakravarti Aravinda
Published: July 2021

Extremes of QT interval are associated with increased risk for sudden cardiac death (SCD), and thus identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous work revealed an association between a common genetic variant in
NOS1AP
and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We thus sought to characterize the effects of
NOS1AP
genetic variants in the multi-ethnic population-based Dallas Heart Study (DHS). Among 3,557 participants in DHS with available DNA, those without QT interval, heart rate, age, and/or sex information, and those with QRS >120 or undetermined ethnicity were excluded, resulting in 2,949 samples available for analysis (501 Hispanic, 1,506 Black, 942 White). Sex- and ethnicity-stratified linear regression was used to correct QT interval for heart rate and age. Eight SNPs spanning the region previously associated with QT interval were genotyped, and ethnic-specific analyses were performed under an additive genetic model. The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in the White participants (+2.6 ms, P<0.005) as well as in Blacks (+3.2 ms, P<3.6 × 10 –5), with the same direction of effect in Hispanics (+1.5 ms, P<0.17). A second SNP, rs16856785, which was uncorrelated with rs16847548 (r2 < 0.01 in Blacks) was also associated with QT interval in Blacks (+1.6 ms, P<0.01), with qualitatively similar results in Whites (+0.9 ms, P<0.33) and Hispanics (+0.6 ms, P<0.66). Adjusting for local and global ancestry using Ancestry Informative Markers did not significantly alter the results. Comparing Blacks homozygous at both SNPs for the QT lengthening allele to Blacks homozygous for the complementary alleles revealed a 13.9 ms difference in QT interval. These data extend the association of genetic variants in
NOS1AP
with QT interval to a Black population, with similar trends in Hispanics. Further, a second, independent site within
NOS1AP
has been implicated in modulating QT interval, highlighting the importance of
NOS1AP
genetic variants in regulating QT interval.
Abstract 4404: Variation in the 4q25 Chromosomal Locus Predicts New-Onset Atrial Fibrillation after Cardiac Surgery
Authors: Body Simon C , Collard Charles D , Shernan Stanton K , Fox Amanda A , Liu Kuang-Yu , Ritchie Marylyn D , Perry Tjorvi E , Muehlschlegel Jochen D , Aranki Sary , Seidman Christine E , Seidman Jonathan G , Donahue Brian S , Hermann Daniel , Lichtner Peter , Meitinger Thomas , Munchen Helmholtz Zentrum , Estrada Juan-Carlos , Pretorius Mias , Ellinor Patrick T , Newton-Cheh Christopher , Brown Nancy J , Roden Dan M , Darbar Dawood
Published: July 2021

Atrial fibrillation (AF) is the most common adverse event following cardiac surgery. A recent genome wide association study identified SNPs associated with AF on chromosome 4q25 adjacent to PITX2, a cardiac transcription factor. However, the role of these genetic variants in post-CABG AF remains unknown. We used clinical and genomic data from 3 major cardiovascular surgical programs to determine the role of 4q25 variants in new-onset postoperative AF. We conducted a prospective observational study of 1,551 consecutive patients undergoing CABG surgery within 3 US centers. Haplotype tagging SNPs encompassing ~300kbp of PITX2 genic region were genotyped. In a discovery cohort of 566 patients, the previously identified SNPs associated with clinical and genomic multivariate predictors of postoperative AF were identified and then assessed in a validation cohort of 985 patients. In the discovery and replication cohorts, 31.4% and 30.0% of patients developed postoperative AF, respectively. A multivariable logistic model of the occurrence of postoperative AF confirmed older age and prior AF to be risk factors for the development of AF. 4q25 SNPs previously associated with ambulatory AF, and other SNPs in linkage disequilibrium described a haplotype that was significantly associated with new-onset postoperative AF. Odds ratio for the associated SNPs ranged between 1.50 and 1.87 (P<10 – 6) in the validation cohort, after accounting for clinical covariates. No SNP within 90kbp of the PITX2 coding region was associated with AF. We have shown in discovery and validation cohorts that non-coding 4q25 SNPs associated with ambulatory AF are also strongly associated with postoperative AF.
Abstract 4405: Sequence Variant for Atrial Fibrillation on Chromosome 4q25 near the PITX2 Gene Increases Risk for Recurrent AF
Authors: Gulcher Jeffrey , Holm Hilma , Gudbjartsson Daniel , Arnar David , Helgadottir Anna , Gretarsdottir Solveig , Thorsteinsdottir Unnur , Stefansson Kari
Published: July 2021

Introduction.
We have previously reported a strong association between two sequence variants on chromosome 4q25 and atrial fibrillation (AF) as the result of a genome-wide association study in Icelandic patients. This association has been replicated in three populations of European descent. About 35% of individuals of European descent have at least one of the variants and the risk of AF increases by 1.72 and 1.39 per copy for the two variants, rs 2200733 and rs10033464, respectively. The purpose of our current analysis was to examine the phenotypes of Icelandic AF patients in relation to the stronger sequence variant, rs2200733.

Methods.
The patients had received the diagnosis of AF at Landspitali University Hospital in Iceland. A genome-wide association scan with 316,000 SNPs on a Illumina BeadChip was performed and medical records were utilized for phenotypic data collection.

Results.
Our data set contained 719 cases with confirmed AF and detailed phenotypic/genotypic data, 435 men and 284 women. Thirty four were homozygous for the stronger genetic variant and 190 heterozygous. The mean age at diagnosis was 69.9 years in the non-carrier group and decreased by 1.9 years for each risk allele (p=0.018). There was a significantly stronger association with lone AF than with AF associated with hypertension or structural heart disease (p=0.042, OR 1.35). There was also a significantly stronger association with recurrent AF as opposed to single episode only (p=0.045, OR 1.47). There was no differential association with stroke but the incidence of stroke diagnosed at time of first presentation with atrial fibrillation was equal in the three groups of homozygous, heterozygous and non-carriers (5.9%, 5.3% and 5.3% respectively) despite younger age of the homozygous individuals.

Conclusions.
Previous analysis demonstrates that the sequence variant rs2200733 is a strong risk factor for AF. This analysis shows that carriers are diagnosed at a younger age and are less likely to have other common AF risk factors such as hypertension and structural heart disease, although the variant increases the risk of AF in all sub-phenotypes. Furthermore, carriers appear more prone to develop recurrent AF.
Abstract 4413: Accelerated Inactivation of the L-type Calcium due to a Mutation in CACNB2b Underlies the Development of a Brugada ECG Phenotype
Authors: Cordeiro Jonathan M , Marieb Mark , Pfeiffer Ryan , Calloe Kirstine , Burashnikov Elena , Antzelevitch Charles
Published: July 2021

Background:
Ion channelopathies are responsible for a number of genetic cardiac arrhythmia syndromes. Recent work demonstrated an association between mutations in CACNA1c and CACNB2b, the genes that encode the α and β subunits of the L-type calcium channel, and the Brugada syndrome (BrS). The mutations previously described all caused a loss of function secondary to a major reduction in peak calcium channel current (I
Ca
). In the present study we describe a novel CACNB2b mutation associated with BrS in which loss of function was caused by accelerated inactivation of I
Ca
.

Methods and Results:
The proband, a 32 yo male, displayed a saddleback ST segment elevation in the right precordial leads that converted to a coved-type ECG following a procainamide challenge. His EP study was positive with double extrastimuli inducing polymorphic VT/VF. He was also diagnosed with vasovagal syncope. Genomic DNA was isolated from blood lymphocytes. All exons and intron borders of 12 ion channel genes were amplified and sequenced. The only mutation uncovered was a missense mutation (T11I) in CACNB2b. The effect of this mutation was studied by expression of WT or T11I CACNB2b in TSA201 cells co-transfected with WT CANCA1c and CACNA2d. Patch clamp analysis showed no difference in I
Ca
density between WT and T11I (17.9±1.8 vs 22.5±4.3 pA/pF, respectively at +20mV). Similarly, steady-state inactivation and channel recovery was not different between WT and T11I mutant channels. However, both the fast and slow decay of I
Ca
produced by T11I mutant were significantly faster compared to WT at potentials between −10 to +30 mV, suggesting a reduction in depolarizing current during the course of an action potential. Application of action potential voltage clamp pulses confirmed that T11I total charge was reduced by 42±2.3% compared to WT (p<0.05).

Conclusion:
We report the first Brugada syndrome mutation in CaCNB2b resulting in accelerated inactivation of the L-type calcium channel. The T11I mutation caused a faster decay of cardiac L-type calcium current but did not significantly alter the magnitude of the peak current. Our results suggest that a reduced total charge carried by I
Ca
during the plateau of the action potential predisposes to the Brugada phenotype.
Abstract 4483: Long-Term Clinical Outcomes of 233 Patients who Presented with Definite/Probable Stent Thrombosis
Authors: Slottow Tina L Pinto , Steinberg Daniel H , Roy Probal , Bonello Laurent , Lemesle Gilles , Kaneshige Kimberly , Xue Zhenyi , Torguson Rebecca , Lindsay Joseph , Pichard Augusto , Satler Lowell , Suddath William O , Kent Kenneth , Waksman Ron
Published: July 2021

Stent thrombosis (ST) is the most concerning adverse outcome of drug-eluting stent (DES) placement. Clinical outcomes of patients experiencing definite and definite/probable ST by the Academic Research Consortium definitions, among the 9535 patients undergoing unrestricted percutaneous coronary intervention (PCI) with DES since April 2003, were examined. Clinical outcomes up to 3 years following DES implant of the patients with definite or probable ST were compared to those without ST. Baseline demographics were similar. The population was 65.7% male with a mean age of 63.7 years. 104 patients presented with 109 definite ST events. 233 patients were adjudicated to have experienced definite or probable ST events, 50 due to unexplained death within 30 days of DES implantation and 79 due to target vessel myocardial infarction with unknown culprit. Outcomes in both these groups were uniformly poorer with a much higher incidence of death, Q-wave myocardial infarction, and target vessel revascularization up to 3 years when compared to patients who did not experience definite or probable ST. (Table

) DES ST is an infrequent, but at 3 years 2/3 of the patients with DES ST are dying and the remaining are experiencing high morbidity.
Abstract 4485: Clinical, Procedural and Angiographic Predictors of Stent Thrombosis Following Drug-Eluting Stent Implantation in Unselected Patients from the Real-World Clinical Practice with Clinical Follow-up (FU) up to 6 Years
Authors: Costa Ricardo A , Sousa Amanda , Moreira Adriana , Costa J. Ribamar , Maldonado Galo , Cano Manuel , Feres Fausto , Mattos Luiz A , Staico Rodolfo , Abizaid Alexandre , Piegas Leopoldo S , Pavanello Ricardo , Barbosa Marcos , Carballo Mariana , Berwanger Otávio , Sousa J. Eduardo
Published: July 2021

DES has demonstrated marked efficacy on reducing restenosis, and therefore TLR, in previous randomized clinical trials compared to bare metal stents. Thus, a widespread use of DES has been observed since their introduction into clinical practice, including treatment of high-risk subgroups. However, recent studies including pts from the “real-world” have raised questions regarding the long-term safety of DES, especially in more complex subsets. Between May/02-Jan/08, 2,365 unselected pts all comers for PCI with DES were prospective enrolled in this single center study. Lesion criteria included ≥1 lesion ≥50% stenosis. Clinical FU was assigned at 1, 6 and 12 months, and yearly up to 6 years (median time: 3.6 yrs). Stent thrombosis (ST) was defined according to the Academic Research Consortium. Overall, 29% of pts had diabetes, 60% multivessel disease, 40% presented with ACS (including 15% AMI). LAD was treated in 43%; 67% of lesions had complex morphology (type B2/C), including 29% mod./severe calcification, 32% eccentric, 5% ostial lesion location, and 5% in-stent restenosis. A total of 3,634 DES were implanted, and 40% had multiple stenting procedure. At late FU (98.3%), overall ST rate was 1.6% (N=38); of that, 61% were definitive (angiographic confirmation), 42% occurred between 1–12 months (late ST), and a fatal event was reported in 47%. By multivariate analysis, ST was associated to: current smoking (HR 2.59; 95%CI 1.18 –5.67; P=0.018), PCI in AMI (HR 3.50; 95%CI 1.31–9.40; P=0.013), multiple steting procedure (HR 1.81; 95%CI 1.09 –3.02; P=0.023), lesion postdilatation (HR 0.50; 95%CI 0.29 – 0.90; P=0.020), eccentric morphology (HR 1.86; 95%CI 1.03–3.34; P=0.039), mod./severe calcium (HR 2.38; 95%CI 1.34 – 4.23; P=0.003), and final residual stenosis by QCA (HR 1.04 per % unit increase; 95%CI 1.01–1.06; P=0.003). In this study, the cumulative incidence of ST up to 6 years clinical FU was very low (1.6%); however, it was associated with a fatal event in half of cases. In this analysis, ST occurred mostly between 1–12 months, and was associated with current smoking, PCI in AMI, multiple stenting, postdilatation, complex lesion morphology including eccentric and significant calcium, and stent underexpansion.
Abstract 4486: Stent Thrombosis After Drug-Eluting Stent Implantation: Incidence, Timing and Relation to Discontinuation of Clopidogrel Therapy Over a 4-Year Period
Authors: Schulz Stefanie , Ellert Julia , Goedel Julia , Byrne Robert A , Iijma Raisuke , Bruskina Olga , Pache Jürgen , Mehilli Julinda , München Deutsches Herzzentrum , Schömig Albert , Kastrati Adnan , München Deutsches Herzzentrum
Published: July 2021

To assess the incidence, timing and relation of drug-eluting stent thrombosis (ST) to discontinuation of clopidogrel therapy. This prospective observational cohort study includes 6816 consecutive patients that underwent a successful drug-eluting stent (DES) implantation between July 2002 through December 2006 in 2 tertiary, high-volume percutaneous coronary intervention (PCI) centers in Germany. The primary end point was definite ST (ARC definition). During 4-year follow-up, 4.2% of the patient population incurred a myocardial infarction (MI), 8.6% had died and 3.1% had experienced a bleeding complication. Definite ST was observed in 73 patients, corresponding to a cumulative incidence of 1.2% at 4 years. Cumulative incidence of ST was 0.5% at 30 days and 0.8% at 1 year. In comparison to patients without ST, patients with ST carried a higher risk of MI (93% versus 3%; OR 48.5 [41.3 to 57.1]) and death (42% versus 8%; OR 5.2 [3.6 to 7.6]). Figure 1

shows the number of patients with ST in each time interval from discontinuation of clopidogrel therapy. Figure 2

depicts the cumulative incidence of ST in patients who were on clopidogrel therapy and in those who discontinued clopidogrel. The 4-year incidence of ST after DES implantation is low in high-volume PCI centers. A relevant number of ST occur early after discontinuation of clopidogrel therapy. The dependence of ST on discontinuation of clopidogrel therapy is evident during the first 6 months but not thereafter.
Abstract 4496: Percutaneous Coronary Intervention in Stable Coronary Heart Disease: Value of Nt-Probnp for Stratification of Long-Term Risk
Authors: Carmo Pedro , Aguiar Carlos , Ferreira Jorge , Raposo Luis , Goncalves Pedro , Almeida Manuel , Teles Rui , Figueira Joao , Machado Francisco , Silva Aniceto
Published: July 2021

Purpose: N-terminal fragment of the B type-natriuretic peptide (NT-proBNP) is an established tool for assessing acute dyspnoea and stratifying risk in heart failure, acute coronary syndromes (ACS), and stable coronary heart disease (SCHD). The aim of this study was to determine the value of NT-proBNP in predicting long-term risk of patients (Pts) submitted to elective percutaneous coronary intervention (PCI) in the setting of SCHD.

Methods: We prospectively studied 291 Pts (age 64.3±9.6 years, 64 female) with SCHD submitted to successful elective PCI, and determined NT-proBNP immediately before PCI. Pts were divided into 2 groups according to NT-proBNP level: group T3 formed by Pts with NT-proBNP level in the highest tertile and group T1+T2 formed by all remaining Pts. The study endpoint was time to the first occurrence of death (D) or non-fatal myocardial infarction (MI) during the mean follow-up of 568 ± 322 days. Multivariable analyses were performed to adjust the prognostic value of NT-proBNP for the effects of factors known to influence NT-proBNP (age, gender, renal function, body mass index) and of other potential predictors of outcome (cardiovascular risk factors, prior cardiovascular events, left ventricular ejection fraction, and PCI characteristics).

Results: NT-proBNP ranged from 5 pg/ml to 104 pg/ml in the 1st tertile (T1), 105 pg/ml to 358 pg/ml in the 2nd tertile (T2), and 364 pg/ml to 33.991 pg/ml in the 3rd tertile (T3). During follow-up, 8 Pts died and 11 suffered a non-fatal MI. NT-proBNP was significantly higher in Pts who experienced an adverse outcome (440 pg/ml [inter-quartile range, 104 –1712] vs 174 pg/ml [inter-quartile range, 78 – 460) in Pts with uneventful follow-up; P= 0.007). An NT-proBNP level ≥364 pg/ml was associated with a higher endpoint rate (13.4% vs 3.1% in group T1+T2) and independently predicted outcome: adjusted hazard ratio 3.11, 95% CI, 1.15– 8.37, P=0.025. The sensitivity, specificity, predictive positive value, and negative predictive value for the criterion NT-proBNP ≥364 pg/ml were 68.4%, 69.1%, 13.4%, and 96.9%, respectively.

Conclusion: In the setting of SCHD, the level of NT-proBNP is a powerful prognostic marker even after successful PCI.
Abstract 4534: Beneficial Effects of Autologous Bone Marrow Cell Infusion in Patients with Chronic Critical Limb Ischemia
Authors: Napoli Claudio , Farzati Bartolomeo , Sica Vincenzo , Silvestroni Andrea , Coppola Giuseppe , Iannuzzi Emanuele , Cacciatore Francesco , Mazzella Francesca , Florio Anna , Matarazzo Angelo
Published: July 2021

Short-term (within 6 weeks follow up) clinical studies indicate that implantation of bone marrow cells (BMCs) into ischemic limbs may improve peripheral ischemia. Here, the long-term safety and feasibility of intrarterial autologous BMCs with oral treatment with antioxidants and L-arginine was investigated in patients with critical ischemia due to advanced atherosclerotic peripheral arterial disease (PAD). The investigation was conformed with the Declaration of Helsinki. We obtained written informed consent from all patients and the Medical Ethics Committee of II University of Naples School of Medicine approved the protocol (March 2005). Moreover, we notified this study to the Italian Ministery of Health and to the NIH-controlled trial register (
NCT00306085
). 18 patients with PAD (advanced III/IV Fontaine stages) were enrolled in this study. An additional group of 18 patients taking maximal drug therapy that refused BMC therapy served as control. The BMC-treated group received two doses of BMCs in the leg arteries (time 0 and 45 days). After 30 days from the first BMC dose, patients received daily antioxidants, and L-arginine. Therapeutic neoangiogenesis was estimated by angiography and laser Doppler\capillaroscopy. Ankle brachial index improvement (ΔABI: >0.1) was seen in 10 patients at 3 months and in 12 patients at 12–18 months. Ischemic ulcers improved in 13 patients (after 6 –12 months). Although 2 underwent amputation, the mean maximum walking distance significantly increased at 3 months and was sustained up to 18 months. Among conservative patients, 10 underwent amputation in comparison to 2 BMC-treated patients. Despite some small published studies employing BMC with a short follow up in PAD patients, we provide the first evidence of long-term safety and feasibility of intrarterial autologous BMC infusion and cotreatment with antioxidants and L-arginine in patients with advanced atherosclerotic PAD. Patients received both BMCs and metabolic treatment to maximize the effect of vitamin E and L-arginine. Results showed significant improvements in the ABI, ulcer healing, maximum walking distance, microcirculation blood flow, and reduction of amputation risk, without any serious adverse reactions until 18 months.
Abstract 4552: Abnormal Cerebrovascular Development in Hypoplastic Left Heart Syndrome During Fetal Life
Authors: Kinnear Caroline , Thompson Megan , Mahmut Naila , Shannon Patrick , Jaeggi Edgar , Chitayat David , Mital Seema
Published: July 2021

Background:
Microcephaly is common in newborns with hypoplastic left heart syndrome (HLHS) possibly related to altered cerebral blood flow during fetal life and may lead to neurocognitive deficits. We assessed cerebrovascular growth in fetuses with HLHS.

Methods:
27 mid-trimester fetuses with autopsy-confirmed HLHS (gestational age, 23±3 weeks; 11 males) without known chromosomal malformations (2002– 07) were included. Body weight (BW) and head circumference (HC) z scores were calculated. Fetal brain sections were studied in 6 HLHS and 5 normal controls. Brain capillary density (von Willebrand factor, vWf), vascular endothelial growth factor (VEGF), and CD133 (stem cell marker) was measured in germinal matrix, intermediate, subcortical and cortical layers.

Results:
Mean BW z score was −0.1±1; HC z score was −0.6±1.4. Capillary density (/hpf) was lower in HLHS vs controls in the germinal matrix (4.1±1.4 vs 7.8 ±1.7; p=0.002) (Fig 1

) and cortex (0.9±0.7 vs 3.5±3.2, p=0.09). Capillaries were larger in the HLHS vs controls (vessel area: 0.059±0.019 vs 0.042±0.016 mm
2
, p=0.005) suggesting reactive dilation to maintain cerebral blood flow. Although VEGF expression was not different between HLHS and controls, the stem cell marker, CD133, was reduced in HLHS (Fig 1

).

Conclusion:
This study demonstrates early onset cerebral growth impairment in fetuses with HLHS. This may be related to reduced stem cells and reduced brain capillary density. Whether antenatal interventions that augment antegrade aortic blood flow can improve vascular development and cerebral growth requires further investigation.

Figure 1:

Brain capillary density (vWF) and CD133 staining was lower in HLHS.
Abstract 4556: Magnetic Resonance Imaging in Evaluating Left Ventricular Rotation and Synchronization in Patients with Congenital Single Ventricle Disease
Authors: Li Xiaokui , Broberg Craig S , Joyce Mary E , Houle Helene , Ashraf Muhammad , Sahn David J
Published: July 2021

Rotational motion of the left ventricular (LV) myocardium has recently received attention as an index of ventricular function. Echocardiographic methods for evaluation of ventricular mechanics are limited by image quality. We developed a method for evaluating cardiac mechanics on gradient cine magnetic resonance imaging (MRI) studies. Twelve adult single ventricle (SV) patients were retroactively selected to compare with 11 randomly selected relatively normal patients who had undergone cardiac MRI study. Detailed SSFP cine images were acquired at several levels in short axis views using Philips and GE MRI systems. Images from each study were evaluated at the apex and papillary muscle levels using VVI (Siemens) for degree of rotation and circumferential strain rate (CSR). Maximal time difference between each segment was recorded as well as the average degree of rotation. When compared with normal patients, SV patients had less rotation at both apex and papillary muscle levels and more dispersion of peak rotation: average rotation: 1.79° ± 0.81° vs. 3.60° ± 1.38°, p < 0.0001, peak rotation: 3.10° ± 1.25° vs 5.71°± 2.63°, p < 0.0001. In contrast, maximum wall motion delay between the segments of each level for data obtained from both rotation and CSR was greater for SV pathology than normals: rotational segment delay, 181.55 ± 76.06 ms vs. 66.86 ± 47.11 ms, p < 0.0001; CSR delay, 90.73 ± 61.98 ms vs. 44.23 ± 37.14 ms, p = 0.004. Average CSR for SV was −8.87 ± 7.30 s
−1
and for normals, −18.02 ± 7.31 s
−1
. Our MRI mechanics study showed decreased CSR in SVs compared to normal LVs, and also a marked decrease in and segmental dyssynchrony of rotation.
Abstract 4557: Validation of Three-Dimensional Echocardiographic Left Ventricular Volumes in Young Pediatric Patients with Complex Congenital Heart Disease: Comparison with Cardiac Magnetic Resonance Imaging
Authors: Friedberg Mark K , Su Xioahong , Tworetzky Wayne , Soriano Brian , Hoch Martin , Marx Gerald R
Published: July 2021

Determination of left ventricular volumes (LVV) is essential for management of infants and small children with complex congenital heart disease (CHD), in particular left heart obstructive lesions. We compared 3-D echo (3DE) LVV in this population to cardiac magnetic resonance (CMR). We prospectively studied children ≤4 y undergoing clinical CMR. Full-volume, subcostal, 3DE data sets were obtained immediately after CMR under similar anesthetic conditions with a 2– 4-MHz matrix-array probe. Endocardial and epicardial borders were manually traced in sequential cross-sectional planes across a minimum of 6 disks. LVVs, mass, and ejection fraction (EF) were subsequently measured on dedicated software using summation of disc methodology. 35 children were studied, including 11 pts with severe LV hypoplasia, median age 7 mo., median weight 7 Kg. Mean vols, mass and EF by 3DE and CMR are shown in the table

. LV diastolic vols and mass by 3DE correlated well with good agreement with MRI. 3DE systolic vols correlated well but were higher than MRI (Table

, Fig

). EF was thus lower by 3DE. 3DE compares well with CMR for evaluation of LV diastolic volumes and mass in young pediatric patients. This will provide essential information to guide clinical management of pts with CHD, especially those with left heart obstructive disease.
Abstract 4570: Association Between Intra-operative and Early Postoperative Glucose Levels and Adverse Outcomes Following Complex Congenital Heart Surgery
Authors: Polito Angelo , Thigarajan Ravi R , Laussen Peter C , Gauvreau Kimberlee , Agus Michael S , Scheurer Mark A , Pigula Frank A , Costello John M
Published: July 2021

Although hyperglycemia is associated with increased mortality in critically ill adults, studies in children undergoing cardiac surgery are limited and have reached conflicting conclusions. We sought to determine whether associations exist between perioperative glucose exposure, prolonged hospitalization and morbid events following complex congenital heart surgery. Metrics of glucose control including average, peak, minimum and standard deviation of glucose levels, and duration of hyperglycemia (hours >126 mg/dL and 200 mg/dL) were determined intraoperatively and for 72 hours following surgery for 378 consecutive children who had a Risk Adjustment in Congenital Heart Surgery-1 category ≥3. Regression analyses were used to determine relationships between glucose variables, hospital length of stay and a composite morbidity-mortality outcome (death, ECMO, infection, hepatic injury, renal failure, and/or brain injury) after controlling for multiple variables known to influence early outcomes. Intraoperatively, a minimum glucose ≤75 mg/dL was associated with greater adjusted odds of reaching the composite morbidity-mortality endpoint (odds ratio [OR], 3.10; 95% confidence interval [CI], 1.49 – 6.48), but other metrics of glucose control were not associated with the composite endpoint or length of stay. Greater duration of hyperglycemia (glucose >126 mg/dl) during the first 72 postoperative hours was associated with longer duration of hospitalization (p<0.001). In the 72 hours after surgery, average glucose <110 mg/dl (OR, 7.30; 95% CI, 1.95–27.25) or >143 mg/dl (OR, 5.21, 95% CI, 1.37–19.89), minimum glucose ≤75 mg/dL (OR, 2.85, 95% CI, 1.38 –5.88), and peak glucose level ≥250 mg/dl (OR, 2.55, 95% CI, 1.20 –5.43) were all associated with greater adjusted odds of reaching the composite morbidity-mortality endpoint. In children undergoing complex congenital heart surgery, intraoperative hyperglycemia was not associated with adverse outcomes. When considering analyses of several metrics of glucose control, the optimal postoperative glucose range may be 110 –126 mg/dl. A randomized trial of strict glycemic control achieved with insulin infusions in this patient population is needed.
Abstract 4580: Proteinuria and Reduced Glomerular Filtration Rate Independently Increase Risk of Thromboembolism in Atrial Fibrillation: The ATRIA Study
Authors: Go Alan S , Fang Margaret C , Udaltsova Natalia , Chang Yuchiao , Borowsky Leila H , Pomernacki Niela K , Singer Daniel E
Published: July 2021

Atrial fibrillation (AF) substantially increases the risk of ischemic stroke but this risk varies among patients with AF. Existing stroke risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for stroke in AF is unknown. In a large, diverse cohort of adults with nonvalvular atrial fibrillation, we examined how chronic kidney disease (i.e., reduced glomerular filtration rate or proteinuria) affects risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Data on patient characteristics, stroke risk factors, longitudinal use of warfarin therapy, and thromboembolic events between 1996 –2003 were ascertained from validated clinical databases. Thromboembolic events (ischemic stroke and other systemic embolism) were confirmed by chart review. We used multivariable Poisson regression to evaluate the independent association between reduced eGFR and documented proteinuria with risk of thromboembolic events off warfarin therapy. During 33,165 person-years off anticoagulation among 13,535 patients with AF and no prior dialysis or renal transplant, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and level of eGFR, proteinuria increased the risk of thromboembolism by 54% (adjusted relative risk [RR] 1.54, 1.28 to 1.84). Independent of proteinuria and other confounders, there was a graded, increased risk of stroke associated with progressively lower eGFR compared with eGFR ≥60 (in units of ml/min/1.73 m
2
): adjusted RR 1.16 (95% CI: 0.95 to 1.40) for eGFR 45– 59, and RR 1.39 (1.12 to 1.71) for eGFR <45 (P=0.001 for trend). Chronic kidney disease increases the risk of thromboembolism in AF independent of other stroke risk factors. Knowing the level of kidney function and presence of proteinuria can potentially improve risk stratification for decision-making about the use of antithrombotic therapy for stroke prevention in AF.
Abstract 4589: Anti-thrombotic Strategies in Patients with Elevated Biomarkers Undergoing PCI: Results from the ACUITY Trial
Authors: Brar Somjot S , McLaurin Brent T , Cox David A , Bertrand Michel E , Lincoff A. Michael , Moses Jeffrey W , White Harvey D , Ohman E Magnus , Mehran Roxana , Lansky Alexandra , Parise Helen , Stone Gregg W
Published: July 2021

Background
: Among patients with non ST-segment elevation acute coronary syndromes (ACS), those with biomarker elevation represent a high-risk cohort. The optimal anticoagulation strategy during PCI in this group remains controversial. We therefore examined the clinical outcomes among biomarker positive patients in the ACUITY trial who underwent PCI.

Methods
: In ACUITY 13,819 patients with ACS were randomized to bivalirudin alone vs. bivalirudin plus glycoprotein IIb/IIIa inhibitor (GPI) vs. heparin plus GPI among; 7,789 patients underwent PCI, of whom 4,687 were biomarker (troponin and/or CKMB) positive. The primary endpoints at 30 days were composite ischemia (death, MI, or unplanned TVR for ischemia), major bleeding not related to CABG, and net adverse clinical events (NACE; composite ischemia or major bleeding).

Results
: Of the biomarker positive patients undergoing PCI, 1,611 were randomized to bivalirudin alone, 1,532 to heparin plus GPI, and 1,544 to bivalirudin plus GPI. The groups were well balanced for age, gender, and major co-morbidities such as diabetes, hypertension, hyperlipidemia, prior MI, renal insufficiency and TIMI risk score (p ≥ 0.1 for all). 30-day and 1 year outcomes are shown. Among the patients pre-treated with a thienopyridine, bivalirudin compared to heparin plus GPI resulted in reduced major bleeding (3.9% vs. 6.8%, p=0.003) and comparable rates of composite ischemia (8.4% vs. 8.1%, p=0.73) and NACE (11.5% vs. 13.1%, p=0.17).

Conclusions
: In biomarker positive ACS patients undergoing PCI, bivalirudin alone suppresses adverse ischemic events to a similar extent as does heparin plus GPI while decreasing major bleeding complications.
Abstract 4595: Intra-arrest Hypothermia Preserves Heart Akt Phosphorylation And Cardiac Function Following Cardiac Arrest In Wild-type But Not Akt(+/−) Mice
Authors: Beiser David G , Wojcik Kimberly R , Zhao Danhong , Hamann Kimm J , Hoek Terry L Vanden
Published: July 2021

OBJECTIVE:
To establish the role of Akt signaling in hypothermia protection following cardiac arrest.

METHODS:
Cardiac arrest was induced in anesthetized C57B6 wild-type (WT) and Akt1(+/−) heterozygous mice with an intravenous bolus of KCl. Animals were randomized to normothermia (
NT
, 37°C) or hypothermia (
HT
, 30°C) induced after 6 minutes of arrest and continued for 1 hour following return of spontaneous circulation (ROSC). After 8 minutes, resuscitation was attempted with chest compressions, mechanical ventilation, and fluid administration. Following ROSC, resuscitated animals were monitored for up to 4 hours. Total Akt and phosphorylated Akt (pAkt at Ser473 and Thr308) levels were measured by Western blot analysis in whole heart lysates from 4-hour survivors and shams (n=4 each group).

RESULTS:
In WT animals, 4-hour survival (HT = 7 of 8, NT = 3 of 8, p < 0.04), cardiac output (p<0.001) and left-ventricular dP/dt
max
(p<0.001) were significantly improved in HT versus NT animals. In addition, hearts from WT animals randomized to HT displayed increased pAkt (Ser473) levels and over 8-fold higher pAkt(Thr308) levels compared to NT and sham groups (p<0.001). These pAkt changes occurred despite total Akt levels remaining unchanged. Baseline hemodynamics prior to arrest were similar between WT and Akt(+/−) animals, while heart Akt1levels were decreased by approximately 40% in Akt(+/−) heterozygous mice. In contrast to WT mice, HT compared to NT had no effect on Akt(+/−) mouse 4-hour survival rates and left-ventricular hemodynamic measures. Compared to HT treated WT mice, Akt(+/−) animals treated with HT displayed significantly lower maximum left-ventricular pressure, stroke volume, and dP/dt
max
by 4 hours post-ROSC (p<0.05).

CONCLUSIONS:
HT improves short-term cardiovascular outcomes and induces signficant heart Akt(Thr308) phosphorylation during the immediate post-ROSC period. The therapeutic benefit of intra-arrest HT on post-ROSC hemodynamics is greatly attenuated in Akt(+/−) animals, suggesting that Akt signaling may play a critical role in mediating HT protection.
Abstract 4603: Home Surveillance Results in Improved Interstage Weight Gain in Infants following the Norwood Operation
Authors: Uzark Karen , Eldridge Paula , Border William , Alfaro Mary Pat , Donley Megan , Anderson Jeffrey , Eghtesady Pirooz , Manning Peter
Published: July 2021

Infants with complex congenital heart disease are at increased risk for malnutrition and poor weight gain. At our institution, infants who undergo Stage I Norwood operation are discharged with a home surveillance (HomeSurv) program which includes weight monitoring. To evaluate the impact of home surveillance on interstage growth, a current cohort of patients enrolled in Home Surv (n=18) was compared to a cohort discharged immediately prior to the implementation of the Home Surv program (n=20). The cohorts were compared using parametric and non-parametric methods as appropriate. Results: Infants underwent Stage I at a median age of 3.5 days (range 1–26), and at a mean weight 3.0 ± 0.4 kg., 26 with a modified Blalock-Taussig shunt and 12 with a right ventricular-to-pulmonary artery shunt. There were 26 males and 12 females. There were no significant differences between the groups with and without HomeSurv with respect to Stage I age, sex, Stage I weight, or shunt type. Stage I discharge weights were similar between the two cohorts (p=0.23) and there was no significant difference in Stage I hospital length of stay (p=0.10). Mean age at Stage II was 5.1 mos in the HomeSurv group and 4.9 mos in the pre-HomeSurv group, (p = 0.63). Mean weight at Stage II was higher in the HomeSurv group, but not statistically significant (5.9 kg vs 5.5 kg, p=0.30). However, weight gain >15 gms/day post Stage I discharge (our minimum weight gain threshold) was achieved by 89% of infants with Home Surv in comparison to 60% of the pre-HomeSurv group, p<.05. Weight gain was not significantly correlated with weight at Stage I, Stage I hospital length of stay, or age at Stage II, and was not significantly different related to shunt type. Conclusion: Home surveillance including weight monitoring following Stage I Norwood positively impacts interstage weight gain. In particular, it appears to confer protection for at-risk infants who fall below the threshold weight gain of 15gms/day. Future studies should explore whether this improved weight gain is an important factor in interstage morbidity and mortality.