Integrated Lactate Is Improved with a Novel Pharmacologic Inducer of the Endogenous Cytoprotective Heat Shock Protein 70I Gga and Potential COVID Applications

Introduction: Lactate is a common biomarker used in multiple surgical subspecialties. No one has previously measured coronary sinus lactate reduction as a result of drug administration. We therefore tested the hypothesis that IV geranylgeranylacetone (GGA), a novel agent used to treat human peptic ulcer disease, would result in reduced coronary sinus lactate production. Method(s): New Zealand adult rabbits (N=5 each) received IV 50 mg/kg GGA 24 hours before intervention, which consisted of Langendorff perfusion, 30 min of global normothermic cardioplegic arrest, followed by reperfusion. Myocardial release of lactate was measured. HSP70 was quantified by western blot. Differences between GGA+ and GGA- groups pre- and post-ischemia were analyzed by unpaired t-tests. Result(s): In the GGA- group, lactate increased immediately at one minute and throughout the duration of reperfusion. However, in GGA+ hearts, lactate also increased at one min of reperfusion but then continued to decrease throughout the remainder of reperfusion. Lactate was significantly less at every time point of reperfusion in GGA+. Integrated lactate area was significantly less throughout reperfusion in GGA+. Conclusion(s): GGA induced caused a marked decrease in coronary sinus lactate release during reperfusion. Simultaneously intravenously GGA induced myocardial HSP70i and reduced myocardial damage. Further study of the effects and mechanisms involved is indicated. Application to other organs is useful as well. Heat shock proteins (HSPS) are also antithrombotic. Given the thrombotic nature of Covid, induction of HSPS may be beneficial in decreasing the cardiac thoracic and vascular complications of Covid and allowing faster resolution of this disease during to vascular complications.

Successful Use of Biventricular Assist Devices in Fulminant Myocarditis

Background Fulminant myocarditis can cause biventricular dysfunction with a mortality rate over 40%. We report a case with severe biventricular failure due to fulminant myocarditis that was successfully supported by left and right ventricular assist devices. Case A 65-year-old woman presented with chest pain, abdominal pain and diarrhea. She was hypotensive and labs revealed elevated troponin-T of 13.5 ng/mL and lactate of 4.3 mmol/L. She was positive for COVID by antigen testing. She was started on multiple vasopressor infusions and admitted to the intensive care unit. Echocardiogram revealed a severely reduced left ventricular ejection fraction of 15% and severe global hypokinesis. The following day, she developed a wide complex tachycardia that was refractory to amiodarone, lidocaine and multiple defibrillation attempts. She was transferred emergently to the cardiac cath lab where coronary angiography revealed an isolated 70% stenosis of the distal left circumflex artery. A Swan-Ganz catheter was placed that yielded a cardiac index by Fick of 1.2 L/min/m2, systemic vascular resistance of 1270 dynesseccm-5 and mixed venous oxygen saturation of 35%. Decision was made to emergently insert an Impella CP device. That evening, she developed complete heart block and transvenous pacing wire was inserted. Due to frequent suction alarms, decision was made to insert ProtekDuo device, which resulted in hemodynamic stabilization. A temporary coronary sinus pacing lead for atrial capture was inserted to improve atrioventricular synchrony. After several days of monitoring, repeat echocardiogram showed complete recovery of biventricular function and Impella CP and ProtekDuo devices were removed. Decision-making The decision of early implantation of ProtekDuo device was made to provide adequate blood flow to the left ventricular assist device for hemodynamic support. In addition, increased atrioventricular synchrony via insertion of temporary coronary sinus pacing wire improved cardiac output. Conclusion Fulminant myocarditis involving biventricular dysfunction can be supported by the use of simultaneous left and right ventricular assist devices.Copyright © 2023 American College of Cardiology Foundation

"Two in One": Rare Case of Dual Left Anterior Descending Artery

Background Coronary artery anomalies are rare with an incidence of 0.3 to 1.3%. Here we are describing an extremely rare anomaly of the left anterior descending artery (LAD) Case A 55-year-old female with covid-related chronic hypoxemic respiratory failure, pulmonary embolism on apixaban and IgG deficiency on IVIG therapy presented with dyspnea and increased oxygen requirement. EKG had no ischemic changes. Troponins were negative. CTPE was negative. TTE showed normal EF with no valvular or wall motion abnormalities. Right ventricular systolic pressure wasn't calculated due to insufficient TR. Decision-making Left and right heart catheterization was negative for coronary artery disease, bridging or pulmonary hypertension but revealed a dual LAD system and an interesting right coronary anatomy as seen below. These findings were confirmed with a coronary CT angiogram (done in the past that we reviewed again). Stress test was negative for ischemia of the apical anterior wall. The patient reported undergoing coronary angiograms multiple times at other institutions before for recurrent chest pains but has not been diagnosed with anomalous coronary artery until current admission. Conclusion This is a rare anomaly that has been not described before (upon our literature review). It is important to recognize dual LAD system as Inability to visualize the additional vessel, especially when the long LAD originates from the right coronary sinus, can be misinterpreted for mid-LAD occlusion. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

PC-578-02 JUNCTIONAL TACHYCARDIA

Background: Junctional ectopic tachycardia (JET) is a rare tachyarrhythmia in adults. The precise site of origin within the AV junction is unknown. Objective: N/A Methods: N/A Results: A 71-year-old male presented with dyspnea on exertion and recently diagnosed tachycardia in March 2021. He had a history of diabetes mellitus, obesity, hypertension, obstructive sleep apnea, and COVID-19 in 2020. A 14-day monitor demonstrated 43% supraventricular ectopy SVE burden and short runs of SVT. He presented for an electrophysiology (EP) study. He presented to the EP lab in sinus rhythm with frequent SVE. Multipolar catheters were placed in the His bundle region, right atrium, coronary sinus, and right ventricle. The SVE beats had the same QRS morphology, and an identical HV interval and His-right bundle activation sequence as in sinus rhythm and no retrograde conduction, consistent with premature junctional complexes (PJCs). Occasional short bursts of junctional tachycardia were noted. Isoproterenol was titrated to a maximum dose of 8 mcg/min. No other SVT was inducible with atrial overdrive pacing or programmed stimulation or with isoproterenol infusion. A 6 mm tip cryoablation catheter was advanced to the right atrium to the anatomical location of the slow pathway in the inferior triangle of Koch using an electroanatomic mapping system (EnSite NavX). Signals immediately prior to ablation (Figure 1) were notable for a pre-potential 26 ms prior to the His with PJCs. Cryoablation was performed at this site (Figure 2) with resolution of the PJCs at the onset of the freeze. After thawing, a second freeze was administered. No further PJCs were noted at baseline or with isoproterenol infusion. Conclusion: JET could originate from anywhere within the AV node or proximal His bundle. The application of cryoablation at a typical AV nodal slow pathway location with a preceding pre- potential and immediate obliteration of PJCs suggests that the origin in this case was from this region rather than a true His bundle extrasystole. Identification of pre-potentials to the junctional ectopy can guide safe ablation of this dysrhythmia. [Formula presented] [Formula presented]

Coronary Sinus Integrated Lactate Decreases After Ischemia and Reperfusion with GGA Induced hsp70

Purpose: Background: Ischemia reperfusion(IR) increases lactate. No one has examined if cardiac-specific coronary sinus lactate(CSL) can be reduced with prior cytoprotective heat shock protein 70(hsp70i) induction. We previous demonstrated improved IR in vivo with inducted hsp70i. Geranylgeranylacetone(GGA), an hsp70i inducer, has never been administered IV preischemically. Interventions to decrease CSL may improve clinical parameters. Methods: Rabbit hearts underwent 30 cold cardioplegic ischemia then 60 min reperfusion. One group received IVGGA 24 hours prior(GGA+) and the other vehicle(GGA-). CSlactate was collected prior to ischemia and throughout reperfusion. We aimed to determine IVGGA effects on myocardial hsp70i and lactate. Hsp70 western blot was performed. Results: Baseline CSlactate was similar between GGA+ and GGA-(Figure 1). Both peaked CSlactate at 1 minute reperfusion. However GGA+ peak was less. At every time point GGA+ was less. GGA+ CSlactate continued to decrease throughout reperfusion however in GGA- CSlactate increased later. Integrated CS lactate area was less for GGA+(Figure 1). Conclusion: In summary, protective IVGGA resulted in five lactate benefits: lactate was less at 1 minute reperfusion peak,decreased faster in early reperfusion, was reduced at all time points, does not have a second rise and lastly results in overall less integrated lactate production in GGA+. GGA induced hsp70. IVGGA may have clinical applications in endothelial protection in IR and COVID.

Impaired coronary flow reserve in athletes with long-term cardiovascular symptoms after COVID-19

Introduction: Cardiovascular symptoms post-acute sequelae of SARS-CoV-2 infection (CV-PASC) have been increasingly recognized, but the underlying pathobiology is unclear. Endothelial and cardiac pericyte ACE2 receptors are important targets of SARS-CoV-2, resulting in virally-induced endothelial activation, which may adversely affect the coronary microvasculature and impair myocardial performance. We hypothesized that athletes with CV-PASC have microvascular and subclinical myocardial dysfunction. Methods: We compared 15 athletes with CV-PASC with 7 control athletes without prior COVID-19 using regadenoson stress cardiac magnetic resonance (CMR). All athletes participated in >6 hours of endurance activities per week. We analyzed CMR volumes, function, global circumferential strain (GCS), late gadolinium enhancement (LGE), and coronary flow reserve (CFR) by coronary sinus method. Values presented as median [IQR]. Results: CMR in CV-PASC athletes occurred 102 [66,123] days post-SARS-CoV-2 infection. There were no differences in chamber volumes, function, or LGE between groups. One CV-PASC athlete had acute myocarditis (7%). CVPASC athletes had decreased CFR compared with control athletes (Figure 1). Multiple CV-PASC participants had CFR below the 95% CI of the controls and reported normal values from the literature (2.9 and 2.5, respectively). GCS was worse in CV-PASC athletes at the base (-23.7% [-21.6,-26.4] vs -31.1% [-27.3,-33.0], p=0.01), mid-LV (-21.5% [-18.5,-22.8] vs -28.5 [-25.4,-29.9], p=0.008), and apex (-27.1% [-24.1,-29.9] vs -30.6% [-27.8,-38], p=0.07), though the apex did not reach statistical significance. Conclusions: This pilot case-control study found CV-PASC athletes had reduced CFR and associated subclinical myocardial dysfunction as assessed by GCS compared to control athletes. These findings suggest coronary microvascular dysfunction related to endothelial injury may mediate CV-PASC symptoms.