Post MI Research Articles

Abstract Tu135: FYCO1 ameliorates cardiac remodeling in response to ischemia by amplifying autophagic flux

Background: Dysregulation of autophagy is known to have detrimental effects on cardiac remodeling. FYCO1, a novel regulator of autophagy mediates the transport of autophagosomes, thereby amplifying autophagic flux. Here, we investigate the impact of FYCO1 on myocardial healing via autophagy modulation. Methods: FYCO1-Tg mice crossed with RFP-EGFP-LC3 reporter mice (FYCO1-TGxRGFP) were utilized to analyze autophagic flux via confocal microscopy following permanent ligation of the left anterior descending artery (LAD) to induce myocardial ischemia. Autophagy activity was evaluated via Western blot of p62 and LC3 II. Macrophage infiltration and apoptosis was assessed by immunofluorescence microscopy, while Masson's Trichrome staining detected fibrosis and infarct size. Cardiac function was determined by echocardiography. Results: FYCO1-TGxRGFP mice displayed significantly enhanced autophagic flux post MI, as evidenced by increased p62 (WT LAD: 2,9±0,4; TG LAD:4,0±0,5) and LC3 II (WT LAD: 1,6±0,2; TG LAD:14,0±1,4) protein levels. Confocal microscopy revealed an accumulation of autolysosomes in WT mice 30 days post MI (WT autophagosomes: 1±0,4; WT autolysosomes: 38,6±3,8), contrasting with the sustained ratio of autophagosomes to autolysosomes in FYCO1-TGxRGFP mice (TG autophagosomes:43,3±5,1; TG autolysosomes: 73,5±12,4), implying the preservation of adequate autophagic flux. FYCO1 overexpression reduced macrophage infiltration into the border zone post MI (WT LAD: 132,4 ±14,3; TG LAD: 18,91±3,7 and inhibited apoptosis induction shown by cleaved caspase7 activity (WT LAD: 64,6±10,1; TG LAD: 9,2±2,1). Moreover, FYCO1-TGxRGFP mice exhibited significantly reduced fibrosis (WT:19,6±1,8%; TG:10,6±1,6%) and infarct size (WT:34,5 ±3,9%; TG:5,5±2%) in the left ventricle (LV), accompanied by marked improvements in global heart function post MI (EF WT: 32,7±3,2%; TG: 56,4±3,9%) compared to WT mice. Conclusion: In conclusion, FYCO1 mitigates adverse consequences of ischemic injury via induction of autophagy and a previously unrecognized role in modulating inflammation in response to myocardial infarction.

Enhancing miR-19a/b induced cardiomyocyte proliferation in infarcted hearts by alleviating oxidant stress and controlling miR-19 release

Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.

Macrophage transcriptome changes in response to cardiac injuries are determined by the type of lesion rather than their ontogenetic nature

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CRC1425 - DFG Introduction Resident macrophages account for 5% of the cells in the healthy heart. In response to cardiac injury, monocytes infiltrate and differentiate into recruited macrophages complementing the original resident macrophage population, and together orchestrate cardiac remodeling. We aim to identify the extent to which macrophage origin, tissue location and type of cardiac injury determine macrophage phenotypes in ischemic and non-ischemic cardiac injuries over time. Results and methods We use a reporter mouse line CX3CR1Yfp CreER/+:R26tdT/+ to visualize and quantify fluxes of resident and recruited macrophages and their respective localizations within the heart following ischemia and reperfusion (I/R) injury and pressure overload after transversal aortic constriction (TAC), respectively. Interestingly, macrophage numbers peaked during the first week post-surgery in both the local/acute and the global/continuous injury models. Initially, recruited macrophages outnumbered the resident macrophage pool within the infarct area but ultimately reached a near 1:1 equilibrium at 4 weeks post I/R injury. In the remote myocardium the 1:1 equilibrium established already during the first week. In TAC-injured hearts, the 1:1 ratio of recruited and resident hearts also established within the first week post-surgery and persisted up to 8 weeks of follow-up even as cardiac function deteriorated. In the infarct, recruited macrophages showed increased cytokine synthesis, defensive response, and cell adhesion pathways during the first week after injury. Many inflammatory pathways remained activated up to day 28 post MI despite simultaneous activation of the anti-inflammatory response. Formerly resident macrophages and their progeny also mounted an immune response throughout the healing process. Unexpectedly, by day 28 post MI when a stable scar had formed, resident and recruited macrophage population transcriptomes converted onto a common, pro-inflammatory steady state phenotype, that differed from their originally divergent gene expression profiles in the healthy heart by over one thousand genes. In the remote zone, however, resident macrophages maintained cellular homeostasis function, unlike recruited macrophages that retained an inflammatory program. Following TAC surgery, transcriptional profiles remained differentially regulated at all time points tested, where recruited subset induced immune response and resident macrophages upregulated tissue remodeling genes. Conclusion Ischemic and non-ischemic cardiac injuries induce a transient peak of monocyte recruitment and macrophage differentiation in and around cardiac lesions which lead to a permanent integration of recruited monocyte-derived macrophages into the pool of tissue resident macrophages – albeit at different paces. The type of injury and macrophage localization within the changing tissue microenvironment determine partial or complete override of ontogenic cell programs.

Lin28a cardiomyocyte-specific modified mRNA translation system induces cardiomyocyte cell division and cardiac repair

The mammalian heart has a limited regenerative capacity. Previous work suggested the heart can regenerate during development and immediately after birth by inducing cardiomyocyte (CM) proliferation; however, this capacity is lost seven days after birth. modRNA gene delivery, the same technology used successfully in the two mRNA vaccines against SARS-CoV-2, can prompt cardiac regeneration, cardiovascular regeneration and cardiac protection. We recently established a novel CM-specific modRNA translational system (SMRTs) that allows modRNA translation only in CMs. We demonstrated that this system delivers potent intracellular genes (e.g., cell cyclepromoting Pkm2), which are beneficial when expressed in one cell type (i.e., CMs) but not others (non-CMs). Here, we identify Lin28a as an important regulator of the CM cell cycle. We show that Lin28a is expressed in CMs during development and immediately after birth, but not during adulthood. We describe that specific delivery of Lin28a into CM, using CM SMRTs, enables CM cell division and proliferation. Further, we determine that this proliferation leads to cardiac repair and better outcome post MI. Moreover, we identify the molecular pathway of Lin28a in CMs. We also demonstrate that Lin28a suppress Let-7 which is vital for CM proliferation, partially due to its suppressive role on cMYC, HMGA2 and K-RAS.

Disease trajectories following myocardial infarction: insights from process mining of 145 million hospitalisation episodes

Abstract The number of survivors of MI has increased dramatically in recent decades, yet knowledge of post-myocardial infarction (MI) disease risk to date is limited. We investigated temporally ordered sequences of all conditions following MI in nationwide electronic health record data through the novel application of process mining. Here, we present, for the first time, the observed sequences of diseases that individuals accrue post MI. We conducted a national retrospective cohort study of all hospitalisations (145,670,448 episodes, 34,083,204 individuals) admitted to NHS hospitals in England (1st January 2008-31st January 2017, final follow up 27th March 2017). Through process mining we identified trajectories of all major disease diagnoses following MI and compared their adjusted relative risk (RR) and all-cause mortality hazard ratios (HR) to a risk-set matched non-MI control cohort using flexible parametric survival models. Among a total of 375,669 (1·1%) MI patients (872,450 episodes) and 1,878,345 (5·5%) matched non-MI patients (4,712,654 episodes), we identified 28,740 unique disease trajectories. The accrual of multiple circulatory diagnoses was more common amongst MI (RR 4·37, 95% CI 4·00-4·77) and conferred an increased risk of death (HR 1·32, 1·14-1·54) compared with matched controls. Further, trajectories featuring neuro-psychiatric diagnoses (including anxiety and depression) in conjunction with circulatory disorders, were markedly more common and had increased mortality post MI (HR ranging from 1·12 to 1·74) compared with non-MI individuals. Pathways involving both circulatory and digestive diseases appeared more frequently in the MI cohort versus matched controls (RR 4·03 [3·87-4·20] to 4·77 [4·28-5·32]). A number of trajectories including disorders of the eye/adnexa were also associated with an increased risk of death compared with matched controls (HR: 1·32, 1·11-1·57), with those eye/adnexa disorders consisting mainly of cataracts (77·6%). This study quantifies the relative risk and mortality burden associated with disease trajectories following MI from a nationwide hospitalisation cohort for the first time. These data show the significant ongoing cardiovascular disease burden following MI, and crucially highlight the excess accrual of neuro-psychiatric diagnoses conferring increased mortality compared with non-MI individuals. These data provide a clear opportunity for early intervention targets, such as increased focus on the psychological and behavioural pathways for survivors of MI, to mitigate ongoing adverse disease trajectories, multimorbidity and premature mortality. Further understanding of the factors contributing to these trajectories is required to facilitate identification of patients in the early post-MI setting who would benefit most from closer follow-up and prompt intervention.Trajectories: primary diseasesTrajectories: primary+secondary diseases

Impact of diabetes status and chronic kidney disease on myocardial infarction mortality among elderly patients - a retrospective analysis of data from an ongoing nationwide registry

Abstract Background Prevalence of diabetes (DM) is rapidly increasing. With high rate of concomitant chronic kidney disease (CKD) in the elderly population the risk of cardiovascular (CV) complications is very high. Purpose Aim of our study was to evaluate the effect of DM status and CKD on mortality among elderly patients after acute myocardial infarction (AMI). Methods EMIR is an ongoing nationwide registry recording data from all patients in Estonia diagnosed with AMI (ICD-10 I21-I22). The study included all patients aged > 65 years who were hospitalized with the first AMI from 2012 to 2019. Data on glycated haemoglobin (HbA1c) in the time frame of 30 days prior to 7 days after admission, estimated glomerular filtration (eGFR) and creatinine levels within 24 hours of admission were obtained from the hospitals’ databases. Mortality data was acquired by linking the database to the Estonian population register. Follow up period lasted until the end of 2021. Prediabetes was defined as HbA1c ≥ 5,7 – 6,4 %, new DM as HbA1c ≥ 6,5 % without previous DM diagnosis. Information about previous DM diagnosis was acquired from EMIR. Statistical analysis was done using Cox proportional hazards regression model adjusted for age, sex, DM status and renal function. Results A total of 8902 patients (50.5 % women) were identified. Among female patients there was a larger proportion of diabetics and patients with lower eGFR (Table 1). We found that 30 day, 1-year and long – term (median 5.5 years) mortality was higher for both newly diagnosed (30 days: HR 1.6 (95 % CI 1.14 – 2.23); 1–year: HR 1.57 (95 % CI 1.25 – 1.99); long–term: HR 1.53 (95 % CI 1.29 – 1.81)) and known DM (30 days: HR 1.39 (95 % CI 1.19 – 1.61); 1–year: HR 1.28 (95 % CI 1.15 – 1.42); long–term: HR 1.47 (95 % CI 1.37 – 1.58)) patients. Prediabetes did not increase post MI mortality. In all follow up periods mortality increased progressively in accordance with declining renal function from eGFR below 59 ml/min/1.73m2 (Figure 1). Conclusions Our study suggests that newly diagnosed and known DM status and CKD have a considerable effect on elderly patients’ mortality after AMI, both in short and long term. Timely diagnosis and treatment of DM and CKD and meticulous secondary prevention can add to lowering mortality after AMI. However, our data also indicates that a more lenient medical management of prediabetes and mild CKD would be adequate for the elderly AMI patients in the current polypharmacotherapy era.Table 1.Figure 1.

Pretreatment with P2Y12 inhibitors and relationship with clinical outcomes in NSTEMI: Analysis of 2 Argentinian registries

Abstract Introduction Pretreatment with P2Y12 inhibitors has been widely studied in the context of NSTEMI patients, with varying results. General consensus is that this strategy should be avoided, unless a long wait time is expected before angiography can be performed. However, it is unclear whether this strategy is associated with a reduction in clinical outcomes, or an increase in bleeding events. Purpose To analyze frequency of pretreatment in NSTEMI in our medium, and association with clinical outcomes. Methods We analyzed the results of two Argentinian acute coronary syndrome registries from 2017 and 2022. We explored incidence of pretreatment, and drug used. We evaluated first through univariate analysis the relationship between pretreatment use and a clinical composite outcome of in hospital events: Myocardial infarction + Mortality + In stent thrombosis + post MI angina + Stroke/TIA. We also explored the relationship of pretreatment with bleeding events (BARC 2 or higher). We later conducted a logistic regression with other clinical variables: Age, gender, diabetes, previous bleeding events, previous MI, aspirin use, anticoagulation, killip-kimball scale and ejection fraction. Results 1297 patients were included in the analysis, after excluding STEMI patients, patients with current use of P2Y12 inhibitors at time of event, and patients who did not undergo angiography. 75.6% were men, 25.6% diabetic, 27,1% smokers, 70.3% hypertensive, and 23.1% had a previous acute coronary syndrome. Mean age was 55.3 years old. Mean GRACE score was 113,5 and CRUSADE 23,8. 44% of patients recieved pretreatment, mostly with clopidogrel (93.5%). Patients that recieved pretreatment were more frequently hypertensive (73.8% vs 67%, p=0.01) and had a higher incidence of previous MI (27% vs 19%, p=0.002). GRACE score was significantly lower in patients that were pretreated (111,5 vs 115, p=0.04). Pretreatment use was significantly associated with a higher incidence of the composite clinical outcome, occuring in 10.1% of patients pretreated and in 6.9% of patients not pretreated (OR 1.56 (1.06-2.3) p=0.02. Bleeding events were numerically more frequent with pretreatment (8.7% vs 5.9%), though did not reach statistical significance (OR 1.51 (0.99-2.3) p=0.054). In multivariate analysis, after adjusting for multiple clinical variables, pretreatment was no longer associated with a higher incidence of clinical outcomes, though also not with a lower incidence (OR 1.4 (0.89-2.3) p=0.13). Discussion Pretreatment, mostly with clopidogrel, did not show a relationship with either benefit or harm with regard to ischemic and bleeding outcomes in NSTEMI patients.

Abstract 15948: Highly Suspicious Yet Diagnostically Unrevealing Left Ventricular Free-Wall Rupture Following STEMI

Introduction: Left ventricular wall rupture is a rare but lethal complication following a ST elevation myocardial infarction (STEMI). We present a case of left ventricular free-wall rupture not identified on echocardiography and CT angiography (CTA) despite high suspicion who underwent emergent lifesaving mediastinal exploration and repair. Case: A 52-year-old male with past medical history of hypertension presented with typical chest pain. He was found to have STEMI with 100% left anterior descending (LAD) artery occlusion and underwent percutaneous coronary intervention to mid LAD. Post procedure, he developed atrial fibrillation with rapid ventricular rate, pericarditis, increasing pericardial effusion (Figure 1), and cardiogenic shock. He underwent intra-aortic balloon pump placement with no improvement in hemodynamics and subsequently an Impella 5.5 was placed. On post MI Day 3, he underwent pericardial window in the setting of shock and increasing pericardial effusion. Intraoperative TEE showed signs of tamponade physiology (Figure 2). Repeat echocardiograms and CTA was unrevealing of a rupture. Post MI day 6, he had increasing output from the drains and increasing pericardial effusion with complete right ventricular collapse on bedside echocardiogram. Emergent mediastinal exploration revealed left ventricular (LV) free-wall rupture which was repaired with a bovine patch. Hemodynamics improved and goal directed medical therapy was started. Discussion: Free wall rupture is a rare complication post MI and is reported in only 0.01% of STEMI. It usually occurs within 1 week, majority occurring within 24 h of MI. Small LV wall rupture can be challenging to diagnose on cardiac imaging. This case emphasizes the importance of having a high index of suspicion for diagnosing free wall rupture in patients presenting with hemodynamically unstable pericardial effusion post STEMI. Prompt pericardiocentesis and surgical intervention lead to a good outcome.

Disease trajectories following myocardial infarction: insights from process mining of 145 million hospitalisation episodes

Knowledge of post-myocardial infarction (MI) disease risk to date is limited-yet the number of survivors of MI has increased dramatically in recent decades. We investigated temporally ordered sequences of all conditions following MI in nationwide electronic health record data through the application of process mining. We conducted a national retrospective cohort study of all hospitalisations (145,670,448 episodes; 34,083,204 individuals) admitted to NHS hospitals in England (1st January 2008-31st January 2017, final follow-up 27th March 2017). Through process mining, we identified trajectories of all major disease diagnoses following MI and compared their relative risk (RR) and all-cause mortality hazard ratios (HR) to a risk-set matched non-MI control cohort using Cox proportional hazards and flexible parametric survival models. Among a total of 375,669 MI patients (130,758 females; 34.8%) and 1,878,345 matched non-MI patients (653,790 females; 34.8%), we identified 28,799 unique disease trajectories. The accrual of multiple circulatory diagnoses was more common amongst MI patients (RR 4.32, 95% CI 3.96-4.72) and conferred an increased risk of death (HR 1.32, 1.13-1.53) compared with matched controls. Trajectories featuring neuro-psychiatric diagnoses (including anxiety and depression) following circulatory disorders were markedly more common and had increased mortality post MI (HR ranging from 1.11 to 1.73) compared with non-MI individuals. These results provide an opportunity for early intervention targets for survivors of MI-such as increased focus on the psychological and behavioural pathways-to mitigate ongoing adverse disease trajectories, multimorbidity, and premature mortality. British Heart Foundation; Alan Turing Institute.

The Impact of Dapagliflozin on Cardiac LV Systolic Function in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention Who Developed Post MI LV Dysfunction

Abstract Aim and objectives To study the impact of dapagliflozin on LV systolic function in patients with ST Elevation Myocardial Infarction undergoing primary percutaneous Coronary Intervention who developed post MI LV dysfunction. Patients and Methods The study included 80 patient who presented with ST-segment elevation myocardial infarction and underwent primary PCI at the catheterization lab unit, Cardiology department, Ain Shams University. The patients were divided into 2 groups. The standard treatment was given to all patients according to the ESC guidelines including: ACEI or ARNi, a beta-blocker, and an MRA[1] uptitrated according to the clinical state of the patient. The study medication was 10 mg of dapagliflozin[1] given once daily in the morning to the case group and a placebo medication to the control group. LVEF was assessed in both groups post primary PCI and at follow-up after 3 months by the same Echo machine GE VIVED S5 after the procedure since first of June 2021 till end of January 2022. Results There were no statistically significant difference between both groups regarding gender distribution, mean age, and the incidence of different risk factors of CAD (smoking, Diabetes and hypertension). Regarding pain to door (PTD) time, there was no statistically significant difference between case and control groups (P-value = 0.695), and anterior STEMI was the most common presentation in both groups (90% in the case group and 77.5% in the control group in the control group). Subsequently, there was no statistically significant difference between case and control groups regarding TIMI flow, and post-MI EF with mean range 34.88% ± 3.55% in the case group and 34.58% ± 3.65% in the control group (P = 0.711). On the other hand, there was statistically significant improvement in follow-up EF in the case group which showed a mean range of 45.36% ± 7.13% in comparison with the control group which showed a mean range of 41.80% ± 6.93% (P = 0.027). Conclusion Dapagliflozin administration in the early phase after STEMI results in significant improvement in LV systolic function in comparison with the placebo. Abbreviations ACE-I: Angiotensin-converting enzyme inhibitor; ACS: Acute coronary syndrome; ARNI: Angiotensin receptor-neprilysin inhibitor; CBC: Complete blood picture; DM: Diabetes Mellitus; ECG: Electrocardiogram; FH: Family History; GLS: Global longitudinal strain; HF: Heart Failure; HFrEF: Heart Failure reduced Ejection Fraction; HTN: Hypertension IV: Intravenous; LV: Left ventricle; LVEF: Left ventricular ejection fraction; MI: Myocardial Infarction; MRA: Mineralocorticoid receptor antagonists; PCI: Primary percutaneous coronary intervention; SD: Standard deviation; SGLT-2: Sodium-glucose cotransporter-2 inhibitors; SPSS: Statistical Package for the Social Science; STEMI: ST-segment elevation myocardial infarction; T2D: Type 2 Diabetes Mellitus

News Brief: β-blockers may not be beneficial one year post MI.

News Brief: β-blockers may not be beneficial one year post MI.

Omega-3 fatty acid supplements and risk of atrial fibrillation and ‘micro-atrial fibrillation’: A secondary analysis from the OMEMI trial

Recent randomized clinical trials have raised concerns regarding potential off target adverse effects from supplementation of n-3 polyunsaturated fatty acids (PUFA) on atrial fibrillation (AF) risk. We aimed to assess risk and potential mediators of AF and 'micro-AF' from n-3 PUFA in post-myocardial infarction (MI) patients. In the OMEMI trial, 70-82 y. o. patients with a recent MI were randomized to 1.8g/day of eicosapentaenoic-/docosahexaenoic acid (EPA/DHA) or placebo (corn oil) for two years. New-onset AF and 'micro-AF' was recorded by clinical detection and by screening with Zenicor thumb-ECG (adjudicated by blinded investigators). Serum EPA and DHA were measured at baseline and study end. At baseline, 759 of 1014 (75%) patients had no AF history. These patients were aged 75±4 years and 71% were male. During follow-up, 43 patients developed new-onset AF (39 clinically-detected and 4 by thumb-ECG screening). In addition, 27 patients had episodes of micro-AF, yielding a total of 70 patients with new-onset AF or 'micro-AF'. In the n-3 PUFA group 46 (11.9%) had AF/'micro-AF' (28 AF, 18 'micro-AF') and in the placebo group 24 (6.5%) had AF/micro-AF (15 AF, 9 micro-AF); HR 1.90 (95%CI 1.16-3.11), P=0.011. Changes in serum EPA (but not DHA) mediated the effect from n-3 PUFA on AF risk, explaining 65% of the association. Supplementation of n-3 PUFA post MI increases the risk of 'micro-AF' and AF, and increases in EPA seems to be an important mediator of the treatment effect from n-3 PUFA on the risk of AF. OMEMI Study; ClinicalTrails.gov identifier: NCT0184194.

Astudy on prognostic significance of neutrophil-lymphocyte ratio in patients with stemi

Atherosclerosis, the clinically manifested form of cardiovascular disease (CVD), mainly accounts for most deaths worldwide. Inflammatory disorders that elevate CVD risk have been associated with circulating inflammatory markers that encompass neutrophil-lymphocyte ratio (NLR), which could be employed as an economical prognostic tool for the diagnosis of the same. Hence, this study focused on assessing the extrapolative implication of NLR among ST-Elevation Myocardial Infarction (STEMI) patients. The observational study included 55 STEMI patients (Mean age – 52.08 years) at Thanjavur medical college (December 2015 to February 2016). The patients were delineated into two groups based on NLR values (high >3.0 and low <3.0). Among the 55 patients, the post-MI complication was observed in 44 subjects, among which 10% of them expressed a high NLR value. A notable proportion of patients displaying arrhythmia and LV dysfunction had higher NLR values.Henceforth, the study reveals the independent and vital prognostic association between NLR and atherosclerosis that could be designated as a reliable marker in the early diagnosis of the disease as well post MI complications.

Effect of Early Coronary Collateral Circulation in Patients with ST Elevation Myocardial Infarction

Background and Aims: Coronary collateral circulation can develop early after STEMI and patients having these coronary collaterals have favorable outcomes. The aim of this study was to evaluate the prognostic impact of coronary collateral circulation in STEMI.
 Methods: This is an observational prospective study of 106 consecutive STEMI patients undergoing Primary PCI admitted and treated at a tertiary cardiac centre from May 2019 to April 2020. Clinical profile, complications at index admission and atone month follow up were analyzed.
 Results: Out of 106 consecutive patients, 50(47%) had early coronary collateral supplying the infarct related artery. The baseline characteristics of the patients in the two groups, with collateral and without collateral, were similar. Among patients with collateral circulation, only 5% had very well developed (Rentrop3) collaterals. The presence of collateral was strongly associated with presence of preexisting angina (p=0.007) and delayed presentation to hospital (p= 0.04). Coronary collateral was more common in non-diabetics, non-anterior wall STEMI and those with mutivessel disease. Compared with the patients without collateral supply, those who had collateral had fewer incidence of in-hospital heart failure (p=0.03) and post MI pericarditis (p=0.04).
 Conclusion: In STEMI, development or recruitment of early collateral supply to the infarct related artery was associated with lower rates of heart failure, post MI pericarditis, cardiogenic shock, hospital stay and in-hospital deaths. At 1 month, patients with collateral supply had fewer angina recurrence, reinfarcton and stent thrombosis.

In Hospital Outcome of Patients with Acute St-Elevation Myocardial Infarction Requiring Temporary Pacemaker

Background and Aim: Acute myocardial infarction is a serious public health concern around the globe and temporary pacing is required in a variety of myocardial infarction. The present study aimed to determine the in-hospital outcome of acute ST elevation myocardial infarction patients requiring a temporary pacemaker. Patients and Methods: This descriptive cross-sectional study was carried out on 120 acute myocardial infarction patients in the Cardiology Unit of PIMS Hospital, Islamabad from January 2021 to March 2023. Each individual underwent chest X-ray, ECG and serum markers. A detailed physical history including age, gender, smoking history, occupation, ischemic heart disease, diabetes, and hypertension were noted in specific designed proforma. Inclusion Criteria: Acute myocardial infarction patients who had chest pain, elevated serum markers, New onset ST Elevation and complete heart block on ECG and required pace maker during their hospitalization were enrolled. Exclusion Crieteria: Complete Heart block due to CKD or electrolyte imbalance, beta blocker or calcium channel blocker overdose, congenital heart block were excluded from the study. Results: The overall mean age was 52.64±6.8 years. The incidence of smokers, diabetes, and hypertension was 76 (63.3%), 56 (46.7%), and 52 (43.3%) respectively. The mean duration of symptom’s onset during hospital admission was 7.9±3.8 hours. About 48 (40%) patients had implanted temporary pacemaker at presentation, 66 (55%) on first post MI day, and 6 (5%) on 2nd post MI day. The in-hospital mortality was 8.3% (n=10). The incidence of ventricular tachycardia, ventricular fibrillation, and asystole was 28.3% (n=34), 3.3% (n=4) and 1.7% (n=2) respectively. Conclusion: The present study found that complete heart block is associated with a poorer early prognosis in individuals with ST-Elevation MI who require temporary pacemaker. In these individuals, a more intensive therapy strategy targeted at reducing early death is required. Keywords: Acute myocardial infarction, in-hospital outcome, temporary pace maker

Individualized assessment and optimization of post myocardial infarction care by introducing a hybrid clinic - A DGH experience

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Optimal secondary prevention remains key in improving cardiovascular outcomes post myocardial infarction. Barriers to achieving timely and individualized medical optimization include unavailability of close follow up’s, compliance to secondary prevention, and more recently, the impact of COVID pandemic on outpatient face to face clinic appointments. With the recent emphasis from the European Society of Cardiology on secondary prevention in addition to optimizing lipid therapy, a dedicated service for post MI patients to address individualized risks can provide a timely opportunity to improve holistic cardiovascular care. Purpose To assess established secondary prevention practices, we initially audited 52 patients who presented with ACS between Jan 2020 and July 2020. These patients were assessed for post MI care optimization at 6 weeks post discharge. Utilizing ESC guidelines as audit targets, in our 6-week post discharge audit, we identified that there was scope of ACE-inhibitor up titration in 55.8% of the patients, beta-blocker optimization in 9.6%, Lipid lowering agents in 15.4%, mineralocorticoid receptor antagonist addition in patients with impaired LV systolic function in 5.8% of the patients. 5% of patients with new diagnosis of diabetes required referral to specialist teams for diabetic medication initiation or optimization. These results provided an opportunity to introduce a structured post MI clinic that will allow individualized risk assessment on an outpatient basis. Method We proposed a one stop hybrid clinic where all patients discharged following a myocardial infarction received a consultation 6 – 8 weeks following a discharge. These patients were sent blood forms 2-3 weeks prior to their appointment for full blood count levels, renal functions, liver profile, HBa1c levels and lipid profile. Focus of this consultation was to assess and educate the patient on risk factors (smoking, diabetes, cardiac rehab program), assess and address compliance to secondary prevention medications and finally titrate medications to maximum tolerated doses whilst achieving ESC defined targets for secondary prevention (post MI target systolic BP<140mmHg in non diabetics and <130mmHg in diabetics, LDLc <1.4, smoking cessation, HBa1c <49). Where appropriately identified, referral to lipid specialist and diabetes specialist teams were made to provide holistic multi-disciplinary management. Results To understand the Impact made by the clinic we obtained patient list through local electronic records to filter those discharged with a primary diagnosis of myocardial infarction in 2022. An audit tool was created and data collection was performed including baseline characteristics as per table 1 and interventions made Table 2. Conclusion(s) By establishing the post MI clinic we were able to demonstrate efficient individualized assessment and optimization of secondary prevention risk factors and pharmacotherapy.

Application of Myocardial Contrast-Enhanced Ultrasound in Heart Transplantation in Patients with Acute Myocardial Infarction：A Case Report

Background: MCE is a safe and effective myocardial perfusion assessment technique; it is used for the assessment of post MI viability. Case Presentation: A 52-year-old male with cardiogenic shock caused by secondary acute myocardial infarction and successful coronary stent implantation with ECMO, IABP and ventilator assistance and with no significant recovery of postoperative cardiac function. The result of MCE was also reported. The allograft was successfully performed 8 days after ECMO-assisted support. The patient was successfully transferred to the general ward 8 days after surgery and successfully discharged on day 86 of admission. Conclusions: ECMO provides effective mechanical assistance support for patients with end-stage heart failure, buys time for heart transplantation surgery, and was an effective cardiopulmonary support treatment. An evaluation of myocardial perfusion and survival quantity was an important reference for emergency heart transplantation.

Wearable cardioverter defibrillator for preventing sudden cardiac death in patients at risk: An updated systematic review of comparative effectiveness and safety.

To synthesise the available evidence of wearable cardioverter defibrillator (WCD) therapy as an add-on measure to optimal medical therapy (OMT) or as a replacement of hospital stay. An update systematic review (SR) of comparative effectiveness and safety of WCD therapy was conducted. We included randomised controlled trials (RCT), prospective comparative studies and prospective uncontrolled studies with at least 100 patients. A narrative synthesis of the evidence was conducted. One RCT (n = 2348) and further eleven observational studies (n = 5345) fulfilled our inclusion criteria. In the only available RCT, the use of the WCD was not statistically associated with a clinical benefit on arrhythmic mortality in post-myocardial infarction (MI) patients with an ejection fraction of ≤35%. The compliance with WCD therapy was low in the RCT and high in observational studies, with ten observational studies reporting on a daily wear time between 20 and 23.5 h. The range of percentage of patients receiving at least one appropriate shock was 1-4.8% and the rate of first shock success was reported to be 100% in three studies. Serious adverse events (SAEs) such as inappropriate shocks occurred rarely, with between 0% and 2% of patients being inappropriately shocked within ten observational studies. In one of the observational studies, two patients (2%) were allergic to nickel developing skin rash and false alarms occurred in 58 patients (57%) in this study. Another registry study (n = 448) reported milder AEs, such as dermatitis and pressure marks, occurring in 0.9% and 0.2% of enrolled patients, respectively. The only available RCT failed to show superiority of add-on use of WCD in post MI patients. Observational evidence shows that the compliance with WCD is good, but the evidence is afflicted with selection bias and the inclusion of diverse mixed patient populations diluting the ability to draw indication-specific conclusions on the utility of the device. More comparative data is needed to justify continuing or expanding use of WCD therapy.

Frequency of LV Thrombus Formation after Anterior Wall St-Segment Acute Myocardial Infarction

Objective: To assess the frequency of thrombus formation in LV post Anterior wall ST Segment elevation acute MI. Methodology: In this descriptive case series during the year 2018 we included 100 cases of age 40-70years of either gender presenting with STEMI planned to undergo Transthoracic echocardiography. Demographic information including name, age, gender, BMI, smoking and diabetes (BSR>186mg/dl) was also noted. Then patients were admitted in cardiology wards and were followed-up there. Then patients were discharged after 3days and were followed-up in OPD for one week. After one week, patients were evaluated on 2-D Transthoracic echocardiography and LV thrombus was labeled. The patients who had LV thrombus, were managed as per hospital protocol. Results: The mean age of patients was 56.68±8.59years. There were 90 (90%) males and 10 (10%) females. The mean BMI of patients was 24.54±3.49kg/m2. There were 43 (43%) smokers and 57 (57%) were non-smokers. There were 36 (36%) diabetics and 64 (64%) were non-diabetics. In this study, 63 (63%) underwent thrombolysis and 87 (87%) underwent primary PCI after STEMI. There were 7 (7%) cases who developed LV thrombus while 93 (93%) were remained free of LV thrombus. Concussion: Frequency of Left ventricular thrombus formation is low in our local population. Keywords: Left ventricular thrombus, anterior wall myocardial infarction, ST-segment elevation myocardial infarction, Transthoracic echocardiography

Myofibroblast Ccn3 is regulated by Yap and Wwtr1 and contributes to adverse cardiac outcomes.

While Yap and Wwtr1 regulate resident cardiac fibroblast to myofibroblast differentiation following cardiac injury, their role specifically in activated myofibroblasts remains unexplored. We assessed the pathophysiological and cellular consequence of genetic depletion of Yap alone (Yap fl/fl ;Postn MCM ) or Yap and Wwtr1 (Yap fl/fl ;Wwtr1 fl/+ ;Postn MCM ) in adult mouse myofibroblasts following myocardial infarction and identify and validate novel downstream factors specifically in cardiac myofibroblasts that mediate pathological remodeling. Following myocardial infarction, depletion of Yap in myofibroblasts had minimal effect on heart function while depletion of Yap/Wwtr1 resulted in smaller scars, reduced interstitial fibrosis, and improved ejection fraction and fractional shortening. Single cell RNA sequencing of interstitial cardiac cells 7 days post infarction showed suppression of pro-fibrotic genes in fibroblasts derived from Yap fl/fl ,Wwtr1 fl/+ ;Postn MCM hearts. In vivo myofibroblast depletion of Yap/Wwtr1 as well in vitro knockdown of Yap/Wwtr1 dramatically decreased RNA and protein expression of the matricellular factor Ccn3. Administration of recombinant CCN3 to adult mice following myocardial infarction remarkably aggravated cardiac function and scarring. CCN3 administration drove myocardial gene expression of pro-fibrotic genes in infarcted left ventricles implicating CCN3 as a novel driver of cardiac fibrotic processes following myocardial infarction. Yap/Wwtr1 depletion in myofibroblasts attenuates fibrosis and significantly improves cardiac outcomes after myocardial infarction and we identify Ccn3 as a factor downstream of Yap/Wwtr1 that contributes to adverse cardiac remodeling post MI. Myofibroblast expression of Yap, Wwtr1, and Ccn3 could be further explored as potential therapeutic targets for modulating adverse cardiac remodeling post injury.