Heparin Dosing During Percutaneous Coronary Intervention and Obesity.

ABSTRACT: Unfractionated heparin is the most common anticoagulant used during percutaneous coronary intervention. Practice guidelines recommend an initial weight-based heparin bolus dose between 70 and 100 U/kg to achieve target activated clotting time (ACT) of 250-300 seconds. The impact of severe obesity on weight-based heparin dosing is not well studied. We performed a retrospective analysis of 424 patients undergoing percutaneous coronary intervention who received heparin for anticoagulation. We collected detailed data on cumulative heparin administration and measured ACT values in this cohort. We performed separate analyses to identify clinical predictors that may affect dose-response curves. There was significant variability in dosing with mean dose of 103.9 ± 32-U/kg heparin administered to achieve target ACT ≥ 250 seconds. Women received higher initial heparin doses when adjusted for weight than men (97.6 ± 31 vs. 89 ± 28 U/kg, P = 0.004), and only 49% of patients achieved ACT ≥ 250 s with the initial recommended heparin bolus dose (70-100 U/kg). Lower heparin dose (U/kg) was required in obese patients to achieve target ACT. In multivariate linear regression analysis with ACT as dependent variable, after inclusion of weight-based dosing for heparin, body mass index was the only significant covariate. In conclusion, there is significant variability in the therapeutic effect of heparin, with a lower weight-adjusted heparin dose required in obese patients.

Cirrhotic cardiomyopathy: Predictors of major adverse cardiac events and assessment of reversibility after liver transplant.

BACKGROUND: Major adverse cardiac events (MACE) are a leading cause of morbidity and mortality after orthotopic liver transplantation (OLT). Cirrhotic cardiomyopathy (CCM), initially described in 2005 and revised in 2019, is a source of MACE in patients after OLT. We sought to identify CCM-related predictors of MACE at one-year follow-up after OLT and assess for reversibility of CCM post-OLT. METHODS: This is a retrospective study of adult patients who underwent OLT between 2009 and 2019. All patients had transthoracic echocardiography pre-and post-OLT. Patients with a left ventricular ejection fraction <50 % pre-OLT were excluded. MACE was defined as death, myocardial infarction, congestive heart failure hospitalization, or cardiac arrest. RESULTS: In total, 131 patients were included in this study, of whom 103 and 23 patients met the 2005 and 2019 criteria, respectively. During the follow-up period, 42 patients had MACE and these patients were more likely to have ascites (p = 0.003), hepatorenal syndrome (p = 0.019), and CCM per 2005 criteria (p = 0.023). There were no significant differences between pre-OLT CCM per 2019 criteria (19 % vs 17 %, p = 0.758) or MELD-Na score (21.24 vs 19.40, p = 0.166) for MACE post-OLT. Per the 2005 criteria, 35 of 103 patients recovered and these patients were less likely to have MACE post-OLT (p = 0.012). Per the 2019 criteria, 13 of 23 patients recovered post-OLT but this low number precluded further statistics. CONCLUSION: The 2005 Montreal criteria for CCM were an independent predictor of MACE at one-year follow-up post-OLT while the 2019 CCC criteria for CCM were not. In addition, the 2005 Montreal criteria were more prevalent when compared to 2019 CCC criteria. Finally, the 2005 Montreal criteria were reversible post-OLT 34 % of the time compared to the 2019 CCC criteria which were reversible 57 % of the time.

Measures of social deprivation and outcomes after percutaneous coronary intervention.

BACKGROUND: Disparities in socioeconomic status are a frequently cited factor associated with worse cardiovascular outcomes. The social deprivation index (SDI) can be used to quantify socioeconomic resources at the population level. OBJECTIVES: The aim of this study was to assess the association of SDI with clinical outcomes following percutaneous coronary interventions (PCI). METHODS: This was a retrospective observational analysis of patients who underwent PCI and were included in a multicenter cardiac catheterization registry study. Baseline characteristics, congestive heart failure (CHF) readmission rates and survival were compared between patients with the highest and lower SDI. SDI was calculated based on the US community survey census tract-level data. RESULTS: Patients within the highest SDI quintile (n = 1843) had more comorbidities and a higher risk of death [hazard ratio (HR): 1.22 (95% confidence interval, CI: 1.1-1.39, p = 0.004); log rank: p = 0.009] and CHF readmission [HR: 1.56 (1.39-1.75, p < 0.001); log rank: p < 0.001) as compared with those in the lower quintiles (n = 10,201) during mean follow-up of 3 years. Increased risk of highest SDI for all-cause mortality and CHF remained significant after adjustment in multivariable analysis for factors associated with highest SDI. CONCLUSIONS: Patients within the highest SDI quintile had a greater proportion of comorbidities as well as higher risk for adverse outcomes as compared with patients with a lower SDI following PCI.

Assessment of Vascular and Valvular Calcification Improves Screening for Coronary Artery Disease Before Liver Transplantation.

Coronary artery disease (CAD) is common in patients with cirrhosis who underwent orthotopic liver transplantation (OLT) evaluation and stress echocardiogram (echo) has a low sensitivity in these patients. This study aimed to assess the impact of vascular and valvular calcification on the ability to identify CAD before OLT. We performed a case-control study of 88 patients with and 97 without obstructive CAD who underwent OLT evaluation. All patients had a preoperative stress echo, abdominal computed tomography, and cardiac catheterization. A series of nested logistic regression models of CAD were fit by adding independent variables of vascular (including coronary) calcification, aortic and mitral valve calcification, age, gender, and history of diabetes mellitus requiring insulin to a baseline model of abnormal stress echo. Compared with stress echo alone, identification of the presence or absence of vascular and valvular calcification on routine preoperative computed tomography and echo improved the diagnostic performance for the detection of CAD based on coronary angiogram when combined with stress echo in patients with cirrhosis who underwent OLT evaluation (area under the curve 0.58 vs 0.73, p <0.001), which is even further improved when age, gender, and history of diabetes mellitus requiring insulin are considered (area under the curve 0.58 vs 0.80, p <0.001). Achieving target heart rate (p = 0.92) or rate-pressure product >25,000 (p = 0.63) did not improve the ability of stress echo to identify CAD. In conclusion, the use of abdominal vascular, coronary artery, and valvular calcification, along with stress echo, improves the ability to identify and rule out obstructive CAD before OLT compared with stress echo alone.

Hepatic Ischemia/Reperfusion Injury After Liver Transplantation Is Not Associated with Early Impairment of Left Ventricular Ejection Fraction.

BACKGROUND Early myocardial dysfunction is a known complication following liver transplant. Although hepatic ischemia/reperfusion injury (hIRI) has been shown to cause myocardial injury in rat and porcine models, the clinical association between hIRI and early myocardial dysfunction in humans has not yet been established. We sought to define this relationship through cardiac evaluation via transthoracic echocardiography (TTE) on postoperative day (POD) 1 in adult liver transplant recipients. MATERIAL AND METHODS TTE was performed on POD1 in all liver transplant patients transplanted between January 2020 and April 2021. Hepatic IRI was stratified by serum AST levels on POD1 (none: <200; mild: 200-2000; moderate: 2000-5000; severe: >5000). All patients had pre-transplant TTE as part of the transplant evaluation. RESULTS A total of 173 patients underwent liver transplant (LT) between 2020 and 2021 and had a TTE on POD 1 (median time to echo: 1 day). hIRI was present in 142 (82%) patients (69% mild, 8.6% moderate, 4% severe). Paired analysis between pre-LT and post-LT left ventricular ejection fraction (LVEF) of the entire study population demonstrated no significant decrease following LT (mean difference: -1.376%, P=0.08). There were no significant differences in post-LT LVEF when patients were stratified by severity of hIRI. Three patients (1.7%) had significant post-transplant impairment of LVEF (<35%). None of these patients had significant hIRI. CONCLUSIONS hIRI after liver transplantation is not associated with immediate reduction in LVEF. The pathophysiology of post-LT cardiomyopathy may be driven by extra-hepatic triggers.

MiR-150 Attenuates Maladaptive Cardiac Remodeling Mediated by Long Noncoding RNA MIAT and Directly Represses Profibrotic Hoxa4.

BACKGROUND: MicroRNA-150 (miR-150) plays a protective role in heart failure (HF). Long noncoding RNA, myocardial infarction-associated transcript (MIAT) regulates miR-150 function in vitro by direct interaction. Concurrent with miR-150 downregulation, MIAT is upregulated in failing hearts, and gain-of-function single-nucleotide polymorphisms in MIAT are associated with increased risk of myocardial infarction (MI) in humans. Despite the correlative relationship between MIAT and miR-150 in HF, their in vivo functional relationship has never been established, and molecular mechanisms by which these 2 noncoding RNAs regulate cardiac protection remain elusive. METHODS: We use MIAT KO (knockout), Hoxa4 (homeobox a4) KO, MIAT TG (transgenic), and miR-150 TG mice. We also develop DTG (double TG) mice overexpressing MIAT and miR-150. We then use a mouse model of MI followed by cardiac functional, structural, and mechanistic studies by echocardiography, immunohistochemistry, transcriptome profiling, Western blotting, and quantitative real-time reverse transcription-polymerase chain reaction. Moreover, we perform expression analyses in hearts from patients with HF. Lastly, we investigate cardiac fibroblast activation using primary adult human cardiac fibroblasts and in vitro assays to define the conserved MIAT/miR-150/HOXA4 axis. RESULTS: Using novel mouse models, we demonstrate that genetic overexpression of MIAT worsens cardiac remodeling, while genetic deletion of MIAT protects hearts against MI. Importantly, miR-150 overexpression attenuates the detrimental post-MI effects caused by MIAT. Genome-wide transcriptomic analysis of MIAT null mouse hearts identifies Hoxa4 as a novel downstream target of the MIAT/miR-150 axis. Hoxa4 is upregulated in cardiac fibroblasts isolated from ischemic myocardium and subjected to hypoxia/reoxygenation. HOXA4 is also upregulated in patients with HF. Moreover, Hoxa4 deficiency in mice protects the heart from MI. Lastly, protective actions of cardiac fibroblast miR-150 are partially attributed to the direct and functional repression of profibrotic Hoxa4. CONCLUSIONS: Our findings delineate a pivotal functional interaction among MIAT, miR-150, and Hoxa4 as a novel regulatory mechanism pertinent to ischemic HF.

Cardiogenic shock following cardiac tamponade and Takotsubo in COVID-19.

Introduction: Takotsubo is often described as stress-induced cardiomyopathy and is a known cause of heart failure. Objective: Review the clinical course of a young coronavirus disease 2019 (COVID-19) patient who developed Takotsubo following cardiac tamponade. Case presentation: A 42-year-old woman presented to the emergency department with fever, altered mental status and hypoxia. She was ultimately found to be in cardiac tamponade and within 2 hours of a pericardiocentesis she developed Takotsubo and was in cardiogenic shock. Her family decided to place her on comfort measures and she died the same day. Discussion: This case illustrates the increasing number of cardiovascular complications being reported in COVID-19 and highlights the importance of clinicians to be aware of these challenges. Conclusion: Here, we report a distinct presentation of cardiogenic shock in a young COVID-19 patient. The rapid onset of her suspected Takotsubo and the severity of her disease were striking features in this case.

Low molecular weight dextran provides similar optical coherence tomography coronary imaging compared to radiographic contrast media.

BACKGROUND: Optical coherence tomography (OCT) coronary imaging requires displacement of red blood cells from the vessel lumen. This is usually accomplished using radiographic contrast. Low molecular weight dextran has low cost and is safe in low volumes. In the present study, we compared dextran with contrast for coronary OCT imaging. METHODS: Fifty-one vessels in 26 patients were sequentially imaged using manual injection of radiographic contrast (iodixanol) and dextran. OCT images were analyzed at 1 mm intervals to determine the image clarity (defined as a visible lumen border > 270°) and to measure the lumen area and lumen diameter. To correct for the refractive index of dextran, the dextran area measurements were multiplied by 1.117 and the dextran length measurements were multiplied by 1.057. RESULTS: A total of 3,418 cross-sections (1,709 with contrast and 1,709 with dextran) were analyzed. There were no complications related to OCT imaging or to contrast or dextran administration. Clear image segments were observed in 97.0% vs. 96.7% of the cross-sections obtained with contrast and dextran, respectively (P = 0.45). The mean lumen areas were also similar: 6.69 ± 1.95 mm(2) with iodixanol vs. 7.06 ± 2.06 mm(2) with dextran (correlation coefficient 0.984). CONCLUSIONS: The image quality and measurements during OCT image acquisition are similar for dextran and contrast. Dextran could be used instead of contrast for OCT imaging, especially in patients in whom contrast load minimization is desired.

Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines.

BACKGROUND: We hypothesize that left-sided low-level vagus nerve stimulation (LL-VNS) can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs. METHODS AND RESULTS: We implanted a neurostimulator in 12 dogs to stimulate the left cervical vagus nerve and a radiotransmitter for continuous recording of left stellate ganglion nerve activity, vagal nerve activities, and ECGs. Group 1 dogs (N=6) underwent 1 week of continuous LL-VNS. Group 2 dogs (N=6) underwent intermittent rapid atrial pacing followed by active or sham LL-VNS on alternate weeks. Integrated stellate ganglion nerve activity was significantly reduced during LL-VNS (7.8 mV/s; 95% confidence interval [CI] 6.94 to 8.66 versus 9.4 mV/s [95% CI, 8.5 to 10.3] at baseline; P=0.033) in group 1. The reduction was most apparent at 8 am, along with a significantly reduced heart rate (P=0.008). Left-sided low-level vagus nerve stimulation did not change vagal nerve activity. The density of tyrosine hydroxylase-positive nerves in the left stellate ganglion 1 week after cessation of LL-VNS were 99 684 µm(2)/mm(2) (95% CI, 28 850 to 170 517) in LL-VNS dogs and 186 561 µm(2)/mm(2) (95% CI, 154 956 to 218 166; P=0.008) in normal dogs. In group 2, the frequencies of paroxysmal atrial fibrillation and tachycardia during active LL-VNS were 1.4/d (95% CI, 0.5 to 5.1) and 8.0/d (95% CI, 5.3 to 12.0), respectively, significantly lower than during sham stimulation (9.2/d [95% CI, 5.3 to 13.1]; P=0.001 and 22.0/d [95% CI, 19.1 to 25.5], P<0.001, respectively). CONCLUSIONS: Left-sided low-level vagus nerve stimulation suppresses stellate ganglion nerve activities and reduces the incidences of paroxysmal atrial tachyarrhythmias in ambulatory dogs. Significant neural remodeling of the left stellate ganglion is evident 1 week after cessation of continuous LL-VNS.

Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs.

BACKGROUND: Little is known about the relationship between intrinsic cardiac nerve activity (ICNA) and spontaneous arrhythmias in ambulatory animals. METHODS AND RESULTS: We implanted radiotransmitters to record extrinsic cardiac nerve activity (ECNA; including stellate ganglion nerve activity and vagal nerve activity) and ICNA (including superior left ganglionated plexi nerve activity and ligament of Marshall nerve activity) in 6 ambulatory dogs. Intermittent rapid left atrial pacing was performed to induce paroxysmal atrial fibrillation or atrial tachycardia. The vast majority (94%) of ligament of Marshall nerve activity were preceded by or coactivated with ECNA (stellate ganglion nerve activity or vagal nerve activity), whereas 6% of episodes were activated alone without concomitant stellate ganglion nerve activity or vagal nerve activity. Paroxysmal atrial fibrillation and atrial tachycardia were invariably (100%) preceded (<5 seconds) by ICNA. Most paroxysmal atrial tachycardia events (89%) were preceded by ICNA and sympathovagal coactivation, whereas 11% were preceded by ICNA and stellate ganglion nerve activity-only activation. Most paroxysmal atrial fibrillation events were preceded only by ICNA (72%); the remaining 28% were preceded by ECNA and ICNA together. Complex fractionated atrial electrograms were observed during ICNA discharges that preceded the onset of paroxysmal atrial tachycardia and atrial fibrillation. Immunostaining confirmed the presence of both adrenergic and cholinergic nerve at ICNA sites. CONCLUSIONS: There is a significant temporal relationship between ECNA and ICNA. However, ICNA can also activate alone. All paroxysmal atrial tachycardia and atrial fibrillation episodes were invariably preceded by ICNA. These findings suggest that ICNA (either alone or in collaboration with ECNA) is an invariable trigger of paroxysmal atrial tachyarrhythmias. ICNA might contaminate local atrial electrograms, resulting in complex fractionated atrial electrogram-like activity.