A case of left atrial compression secondary to angioedema.

Angioedema due to angiotensin-converting enzyme (ACE) inhibitors is an uncommon, but deadly adverse reaction with an overall incidence of 0.1%-0.2%. Rapid accumulation of interstitial fluid and vasodilation classically involves the mucus membranes of the mouth and face but has the ability to affect other areas. We describe a case of angioedema secondary to ACE inhibitor that affected the esophagus causing left atrial compression and hemodynamic compromise.

A comprehensive meta-analysis of randomized controlled trials comparing drug-eluting stents with bare-metal stents in saphenous vein graft interventions.

BACKGROUND: Several large randomized controlled trials (RCTs) have proven the superiority of drug-eluting stents (DESs) over bare-metal stents (BMSs) for native coronary stenosis. However, RCTs comparing DESs with BMSs for SVG lesions have predominantly been small in size and have yielded conflicting results. Therefore, we conducted an updated comprehensive meta-analysis of RCTs comparing DESs versus BMSs for SVG interventions using the largest sample size to date. METHODS: Scientific databases and websites were searched to find RCTs. Data from six RCTs involving 1,582 patients were included. Pooled risk ratios (RRs) were calculated using random-effects models. The primary outcome of this meta-analysis was target vessel revascularization (TVR). The secondary outcomes were major adverse cardiac events (MACEs), myocardial infarction (MI), stent thrombosis, all-cause mortality, and cardiac mortality. RESULTS: Data from six RCTs involving 1,582 patients were included. Saphenous vein graft interventions with DESs reduced TVR (RR, 0.52; 95% CI, 0.30-0.88; P = 0.017) and MACE rate (RR, 0.60; 95% CI, 0.42-0.87; P = 0.007) compared to BMSs. No difference between the stents were found in rates of MI (RR, 0.69; 95% CI, 0.43-1.10; P = 0.123), stent thrombosis (RR, 0.61; 95% CI, 0.27-1.41; P = 0.255), all-cause mortality (RR, 1.13; 95% CI, 0.74-1.71; P = 0.554), or cardiac mortality. CONCLUSION: For SVG intervention, the MACE rate was lower for DESs compared to BMSs, driven primarily by decreased non-MI-related TVR. Rates of MI, all-cause mortality, cardiac mortality, and stent thrombosis were not different between the stents.

Atrophied cardiomyocytes and their potential for rescue and recovery of ventricular function.

Cardiomyocytes must be responsive to demands placed on the heart's contractile work as a muscular pump. In turn, myocyte size is largely dependent on the workload they perform. Both hypertrophied and atrophic myocytes are found in the normal and diseased ventricle. Individual myocytes become atrophic when encumbered by fibrillar collagen, such as occurs at sites of fibrosis. The mechanisms include: (a) being immobilized and subject to disuse with ensuing protein degradation mediated by redox-sensitive, proteolytic ligases of the ubiquitin-proteasome system and (b) dedifferentiated re-expressing fetal genes induced by low intracellular triiodothyronine (T3) via thyroid hormone receptor ß1. This myocyte-selective, low T3 state is a consequence of heterocellular signaling emanating from juxtaposed scar tissue myofibroblasts and their secretome with its de novo generation of angiotensin II. In a paracrine manner, angiotensin II promotes myocyte Ca(2+) entry and subsequent Ca(2+) overload with ensuing oxidative stress that overwhelms antioxidant defenses to activate deiodinase-3 and its enzymatic degradation of T3. In the failing heart, atrophic myocytes represent an endogenous population of viable myocytes which could be rescued to augment contractile mass, reduce systolic wall stress (afterload) and recover ventricular function. Experimental studies have shown the potential for the rescue and recovery of atrophic myocytes in rebuilding the myocardium--a method complementary to today's quest in regenerating myocardium using progenitor cells.

A Case of Isolated Coronary Artery Ectasia in the Setting of Chronic Inflamation From human Immunodeficiency Virus Infection.

Coronary artery ectasia also known as dilated coronopathy is a relatively rare finding that is most commonly associated with atherosclerosis. Several alternative reasons including congenital malformations and chronic inflammation have been identified as a cause of CAE. In this case, we discuss a 61-year-old male with postoperative chest pain who was found to have localized CAE in the absence of significant atherosclerosis. We also elucidate the recently proposed markers of chronic inflammation that might be associated with coronary artery ectasia.

Novel role for p21-activated kinase 2 in thrombin-induced monocyte migration.

To understand the role of thrombin in inflammation, we tested its effects on migration of THP-1 cells, a human monocytic cell line. Thrombin induced THP-1 cell migration in a dose-dependent manner. Thrombin induced tyrosine phosphorylation of Pyk2, Gab1, and p115 RhoGEF, leading to Rac1- and RhoA-dependent Pak2 activation. Downstream to Pyk2, Gab1 formed a complex with p115 RhoGEF involving their pleckstrin homology domains. Furthermore, inhibition or depletion of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, or Pak2 levels substantially attenuated thrombin-induced THP-1 cell F-actin cytoskeletal remodeling and migration. Inhibition or depletion of PAR1 also blocked thrombin-induced activation of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2, resulting in diminished THP-1 cell F-actin cytoskeletal remodeling and migration. Similarly, depletion of Gα12 negated thrombin-induced Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2 activation, leading to attenuation of THP-1 cell F-actin cytoskeletal remodeling and migration. These novel observations reveal that thrombin induces monocyte/macrophage migration via PAR1-Gα12-dependent Pyk2-mediated Gab1 and p115 RhoGEF interactions, leading to Rac1- and RhoA-targeted Pak2 activation. Thus, these findings provide mechanistic evidence for the role of thrombin and its receptor PAR1 in inflammation.

Protein kinase N1 is a novel substrate of NFATc1-mediated cyclin D1-CDK6 activity and modulates vascular smooth muscle cell division and migration leading to inward blood vessel wall remodeling.

Toward understanding the mechanisms of vascular wall remodeling, here we have studied the role of NFATc1 in MCP-1-induced human aortic smooth muscle cell (HASMC) growth and migration and injury-induced rat aortic wall remodeling. We have identified PKN1 as a novel downstream target of NFATc1-cyclin D1/CDK6 activity in mediating vascular wall remodeling following injury. MCP-1, a potent chemoattractant protein, besides enhancing HASMC motility, also induced its growth, and these effects require NFATc1-dependent cyclin D1 expression and CDK4/6 activity. In addition, MCP-1 induced PKN1 activation in a sustained and NFATc1-cyclin D1/CDK6-dependent manner. Furthermore, PKN1 activation is required for MCP-1-induced HASMC growth and migration. Balloon injury induced PKN1 activation in NFAT-dependent manner and pharmacological or dominant negative mutant-mediated blockade of PKN1 function or siRNA-mediated down-regulation of its levels substantially suppressed balloon injury-induced smooth muscle cell migration and proliferation resulting in reduced neointima formation. These novel findings suggest that PKN1 plays a critical role in vascular wall remodeling, and therefore, it could be a promising new target for the next generation of drugs for vascular diseases, particularly restenosis following angioplasty, stent implantation, or vein grafting.

Novel role of proline-rich nonreceptor tyrosine kinase 2 in vascular wall remodeling after balloon injury.

OBJECTIVE: To investigate the role of Pyk2, a proline-rich nonreceptor tyrosine kinase, in G protein-coupled receptor agonist, thrombin-induced human aortic smooth muscle cell growth and migration, and injury-induced vascular wall remodeling. METHODS AND RESULTS: Thrombin, a G protein-coupled receptor agonist, activated Pyk2 in a time-dependent manner and inhibition of its stimulation attenuated thrombin-induced human aortic smooth muscle cell migration and proliferation. Thrombin also activated Grb2-associated binder protein 1, p115 Rho guanine nucleotide exchange factor, Rac1, RhoA, and p21-activated kinase 1 (Pak1) and interference with stimulation of these molecules attenuated thrombin-induced human aortic smooth muscle cell migration and proliferation. In addition, adenovirus-mediated expression of dominant negative Pyk2 inhibited thrombin-induced Grb2-associated binder protein 1, p115 rho guanine nucleotide exchange factor, Rac1, RhoA and Pak1 stimulation. Balloon injury also caused activation of Pyk2, Grb2-associated binder protein 1, p115 rho guanine nucleotide exchange factor, Rac1, RhoA, and Pak1 in the carotid artery of rat, and these responses were sensitive to inhibition by the dominant negative Pyk2. Furthermore, inhibition of Pyk2 activation resulted in reduced recruitment of smooth muscle cells onto the luminal surface and their proliferation in the intimal region leading to suppression of neointima formation. CONCLUSIONS: Together, these results demonstrate for the first time that Pyk2 plays a crucial role in G protein-coupled receptor agonist thrombin-induced human aortic smooth muscle cell growth and migration, as well as balloon injury-induced neointima formation.

Case Report of Novel, Automatic Shocking Vector Adjustment Algorithm: A Life-Saving Feature of a Modern Defibrillator.

BACKGROUND: Failed delivery of appropriate shocks against fatal dysrhythmias can be the result of low impedance on high-voltage leads. This malfunction might be missed on routine interrogation. We describe the case of a 66-year-old man with a high-voltage lead short circuit who was successfully rescued with the use of an overcurrent detection and automatic shocking vector adjustment algorithm. CASE REPORT: A 66-year-old man with severe nonischemic cardiomyopathy was admitted after receiving 2 shocks from his cardiac resynchronization therapy cardioverter-defibrillator. Interrogation of his defibrillator confirmed 2 consecutive episodes of ventricular fibrillation. For each episode, the initial shock therapy was aborted due to low impedance (<10 ohms) detected on the default shocking configuration: right ventricle to superior vena cava/implantable cardioverter generator. As a result, the device algorithm excluded the superior vena cava coil and immediately delivered a shock of 40 joules between the right ventricular coil and the cardiac resynchronization therapy cardioverter-defibrillator implantable cardioverter generator. This successfully terminated the ventricular fibrillation. All other lead measurements were normal. CONCLUSION: High-voltage lead malfunctions can lead to failed therapy of life-threatening dysrhythmias. Malfunctions like a low impedance of high-voltage leads may not be detected on routine interrogation. Fortunately, the overcurrent detection algorithm recognized the low impedance, and another shocking configuration was selected and successfully terminated the ventricular dysrhythmias. With these algorithms, overcurrent detection and automatic shocking vector adjustment, this patient was rescued. We suggest this feature be considered in all modern defibrillators.

Ablation Therapy for Persistent Atrial Fibrillation.

Atrial Fibrillation (AF) is the most common form of electrical disturbance of the heart and contributes to significant patient morbidity and mortality. With a better understanding of the mechanisms of atrial fibrillation and improvements in mapping and ablation technologies, ablation has become a preferred therapy for patients with symptomatic AF. Pulmonary Vein Isolation (PVI) is the cornerstone for AF ablation therapy, but particularly in patients with AF occurring for longer than 7 days (persistent AF), identifying clinically significant nonpulmonary vein targets and achieving durability of ablation lesions remains an important challenge.

Vagal milieu or electrophysiologic substrate? The link between atrial fibrillation and obstructive sleep apnea.

Atrial fibrillation is the most common cardiac arrhythmia with its prevalence expected to increase to 12.1 million people in the United States by 2030. Chronic underlying conditions that affect the heart and lungs predispose patients to develop atrial fibrillation. Obstructive sleep apnea is strongly associated with atrial fibrillation. Several pathophysiological mechanisms have been proposed to elucidate this relationship which includes electrophysiological substrate modification and the contribution of the autonomic nervous system. In this comprehensive review, we highlight important relationships and plausible causality between obstructive sleep apnea and atrial fibrillation which will improve our understanding in the evaluation, management, and prevention of atrial fibrillation. This is the most updated comprehensive review of the relationship between obstructive sleep apnea and atrial fibrillation.

Beyond Ejection Fraction: Novel Clinical Approaches Towards Sudden Cardiac Death Risk Stratification in Patients with Dilated Cardiomyopathy.

Implantable Cardioverter-Defibrillator (ICD) therapy is indicated for patients at risk for sudden cardiac death due to ventricular tachyarrhythmia. The most commonly used risk stratification algorithms use Left Ventricular Ejection Fraction (LVEF) to determine which patients qualify for ICD therapy, even though LVEF is a better marker of total mortality than ventricular tachyarrhythmias mortality. This review evaluates imaging tools and novel biomarkers proposed for better risk stratifying arrhythmic substrate, thereby identifying optimal ICD therapy candidates.

Ablation Success in Various Arrhythmias: When It Is Appropriate to Recommend Ablation?

Cardiac arrhythmia is an abnormal electrical activity of the heart. It can be divided into rhythms with increased electrical activity (tachyarrhythmia) and those with reduced electrical activity (bradyarrhythmia). Ablation therapy has a role in tachyarrhythmia, but this role varies from being limited in inappropriate sinus tachycardia to being a class 1 indication in typical atrial flutter. A balanced approach in recommendation for ablation therapy for the management of tachyarrhythmias involves knowledge of the interplay between the risk, benefit, success rate, and alternatives with advances in mapping and ablation therapy.

Outcomes of Early Versus Delayed Transcatheter Closure of Post-Myocardial Infarction Ventricular Septal Defect.

BACKGROUND: Post myocardial infarction ventricular septal defect (VSD) is a rare, but devastating complication which carries a poor prognosis if left untreated. Optimal therapy remains unclear and surgical repair is associated with high mortality. OBJECTIVE: The aim of our study is to compare 30-day survival in patients with early versus late primary transcatheter repair of post myocardial infarction ventricular septal defect. METHODS: We performed a comprehensive search of published data through SCOPUS and identified published reports of primary transcatheter closure of post myocardial infarction VSD. We included case reports and series that reported timing of VSD closure and 30-day survival and excluded those with prior surgical repair. Early repair was defined as transcatheter closure within 14 days of diagnosis of VSD while late repair was defined as transcatheter closure after 14 days of diagnosis of VSD. RESULTS: A total 27 publications describing 193 patients were identified in the SCOPUS search. We excluded 8 publications with no reported timing of VSD repair or 30-day outcome. Of the 193 patients initially included, a total of 126 patients fulfilled all the criteria and were included in the final analysis. The overall 30-day survival rate was found to be 62.7% (79 patients). In the early repair group, only 36.2% of the patients were still alive at 30 days compared to 85.3% in the delayed repair group, P < .01. No significant difference in age, gender, presence of shock, VSD size, presence of significant residual shunt, location of VSD or infarction was observed. The early repair group was found to have a significantly larger Qp: Qs ratio as well as larger occluder size and lower rate of successful repair. CONCLUSION: Compared to the late repair group, the early transcatheter VSD repair group had a larger pre-procedure Qp:Qs and worse 30-day survival. Further studies are needed to determine the optimal timing of transcatheter repair of a post myocardial infarction VSD.

Outcomes of transcatheter aortic valve replacement in bicuspid aortic valve stenosis.

BACKGROUND: Due to abnormal valve geometry, patients with bicuspid aortic valve (BAV) have been excluded in many transcatheter aortic valve replacement (TAVR) trials resulting in very limited data with regards to its safety and efficacy. METHODS: We searched electronic databases including Cochrane Database of Systematic Reviews, MEDLINE and EMBASE for all studies including case series, and original reports published before December 2018 that assessed outcomes following TAVR in BAV stenosis. We also included studies that had patients with TAV for comparison. Pooled effect size was calculated with a random-effect model and weighted for the inverse of variance, to compare outcomes post-TAVR between BAV and TAV. The heterogeneity of effect estimates across the studies was assessed using I2. Publication bias was assessed with funnel plots. Statistical analysis was performed using SPSS version 24 (IBM Corp., SPSS Statistics for Windows, Version 24.0. Armonk, NY.). RESULTS: A total of 19 studies describing 1,332 patients with BAV and 3,610 with TAV. There was no significant difference in the30-day mortality between patients with BAV and TAV [odds ratio (OR): 1.18, 95% confidence interval (CI): 0.7-1.7, P=0.41, I2=0]. One-year mortality rate in the BAV population was 13.1% compared to 15.4% in the TAV patients (P=0.75). Patients with BAV had significantly more moderate to severe paravalvular leak (PVL) post TAVR (PVL ≥3) 8.8% vs. 4.2% in TAV patients (OR: 1.478, 95% CI: 1.000-2.184, P=0.050, I2=0. Device success was significantly higher in TAV patients compared to BAV patients 93.5% vs. 87% (OR: 0.63, 95% CI: 0.49-0.86, P=0.003). CONCLUSIONS: TAVR in patients with BAV is associated with a high incidence of paravalvular regurgitation with a comparable 30-day mortality rate to TAV patients. The use of newer generation valve prosthesis improved outcomes.

Cocaine Positivity in ST-Elevation Myocardial Infarction: A True or False Association.

INTRODUCTION: Every year, more than 500,000 US Emergency Department visits are associated with cocaine use. People who use cocaine tend to have a lower incidence of true ST-elevation myocardial infarction (STEMI). OBJECTIVE: To identify the factors associated with true STEMI in patients with cocaine-positive (CPos) findings. METHODS: We retrospectively analyzed 1144 consecutive patients with STEMI between 2008 and 2013. True STEMI was defined as having a culprit lesion on coronary angiogram. Multivariate and univariate analyses were used to identify risk factors and create a predictive model. RESULTS: A total of 64 patients with suspected STEMI were CPos (mean age 53.1 ± 11.2 years; male = 80%). True STEMI was diagnosed in 34 patients. Patients with CPos true STEMI were more likely to be uninsured than those with false STEMI (61.8% vs 34.5%, p = 0.03) and have higher peak troponin levels (21.1 ng/mL vs 2.12 ng/mL, p = < 0.01) with no difference in mean age between the 2 groups (p = 0.24). In multivariate analyses, independent predictors of true STEMI in patients with CPos findings included age older than 65 years (odds ratio [OR] = 19.3, 95% confidence iterval [CI] = 1.2-318.3), lack of health insurance (OR = 4.9, 95% CI = 1.2-19.6), and troponin level higher than 0.05 (OR = 24.0, 95% CI = 2.6-216.8) (all p < 0.05). A multivariate risk score created with a C-statistic of 82% (95% CI = 71-93) significantly improved the identification of patients with true STEMI. CONCLUSION: Among those with suspected STEMI, patients with CPos findings had a higher incidence of false STEMI. Older age, lack of health insurance, and troponin levels outside of defined limits were associated with true STEMI in this group.

Cannabinoids and Symptomatic Bradycardia.

Cannabinoids, the bioactive components of marijuana, have adverse cardiovascular consequences, including symptomatic sinus bradycardia, sinus arrest and ventricular asystole. Physicians should be aware of these deleterious consequences which can appear in otherwise healthy persons who are chronic marijuana users.

Stress-induced thrombus: prevalence of thromboembolic events and the role of anticoagulation in Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TCM), also known as stress-induced cardiomyopathy has a favorable prognosis with expected recovery in weeks. Left ventricular (LV) thrombus is a known complication of TCM, which can lead to embolization and potentially a stroke. The prevalence of LV thrombus and the role of anticoagulation have yet to be fully defined in this condition. METHODS: We performed a search of published literature through PubMed and Scopus, which identified 282 patients with TCM in whom the incidence of LV thrombus and/or thromboembolic event was reported. In order to contrast this to the current anticoagulation strategy of atrial fibrillation, the occurrence of LV thrombus was compared to the adjusted stroke rate using the CHADS2 score. RESULTS: Of the 282 patients identified through a literature search, 26 (9.2%) were noted to have a thromboembolic event in the setting of TCM. The incidence of thromboembolic event ranged from 5.3% to as high as 14.3%. When compared to the CH2sDS2-VASc score, the average incidence of LV thrombus in our study equated to a score between 4 and 5. CONCLUSIONS: While the occurrence of LV thrombus in TCM is variable among studies, the average incidence remains relatively high. Thus, making LV thrombus a significant complication of stress-induced cardiomyopathy. Prophylactic anticoagulation until recovery may have a role in reducing the rate of LV thrombus. Further studies will be needed to determine the rate of embolization and utility of anticoagulation in TCM.

Simultaneous acute cardio-cerebral infarction: is there a consensus for management?

Acute ischemic stroke (AIS) and acute myocardial infarction (AMI) are both life-threatening medical conditions with narrow therapeutic time-window that carry grave prognosis if not addressed promptly. The acute management of both condition is well documented in the literature, however the management of a simultaneous presentation of both AIS and AMI is unclear. A delayed intervention of one infarcted territory for the other may result in permanent irreversible morbidity or disability, and even death. In addition, the use of antiplatelet and anticoagulants that are inherently part of an AMI management may increase the risk for hemorrhagic conversion associated with intravenous thrombolysis used in AIS, and the use of a thrombolytic in AIS increases the risk of cardiac wall rupture in the setting of an AMI. Despite this ambiguity, there is no clear evidence-based guideline or clinical studies that have addressed the optimal management of this rare co-occurrence. This review paper examines the existing literature on the management of simultaneous acute cardio-cerebral infarction (CCI) and highlights the existing challenge to management.