Beta-blockers in post-myocardial infarction patients: refractive errors in reading the evidence.

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Insufficient compliance with current implantable cardioverter defibrillator (ICD) therapy guidelines in post myocardial infarction patients is associated with increased mortality

Background: Tachycardia and heart failure are a major concern in post myocardial infarction (PMI) patients and a therapeutic challenge. Beta blockers, the first choice drugs used have certain disadvantages. Ivabradine known to reduce heart rate was compared with Metoprolol for their benefits and side effects. The aim of the study is to analyze the effects of Ivabradine on heart rate and LVEF in comparison with Metoprolol at fixed doses over a period of 12 months from the time of discharge. Methods: 278 MI patients were grouped and observed for 12 months for the effect of Ivabradine and Metoprolol drugs on their heart rate (HR) and LVEF values. Patients with acute inferior wall STEMI, HR above 70/minute were included. All patients were on treatment for 12 months. Patients likely to develop cardio-pulmonary complications excluded. MI was confirmed on ECG and serial CK-MB/ troponin T measurements and 2D ECHO. Patients were with Holter monitors. Results: 278 patients were grouped as Ivabradine group wherein 138 patients (Ivabradine 5mg twice daily) and Metoprolol group 140 patients (Metoprolol 25 mg twice daily). All the risk factors were similar in both the groups. The mean HR and LVEF values were similar in both the groups. The range of HR was 64 to 86 beats per minute in all patients. The symptomatologies among the patients of both the groups were also similar. Reduction of HR was from 76.43±7.3 to 62.55±1.05 and in Metoprolol group from 77.51±4.50 to 61.45±2.35 beats per minute 13 (09.24%) patients from Ivabradine group and 19 (13.57%) patients from Metoprolol group showed a heart rate less than 60/bpm, others had heart beats > 60/mt. Conclusion: Ivabradine was a competitive bradycardic drug in comparison to Metoprolol in early Post MI patients. It had similar action on LVEF as Metoprolol. It could be potentially used an alternative anti-tachycardia drug with no other cardiovascular side effects and wherever â-blockers are contraindicated. Bangladesh J Medicine 2022; 33: 252-258

Substantial changes occurred in the core components of cardiac rehabilitation (CR) during the 1990s and first decade of the new millennium. These changes have raised concerns about the relevance of findings from earlier studies on the effect of early outpatient CR (Phase 2 CR) on various outcome measures, including self-reported health status. PURPOSE: In this multicenter study, we investigated the effect of a contemporary phase 2 CR program on self-reported health status in 4,791 post-myocardial infarction patients (Group A, n=2,154) versus post-coronary artery bypass graft surgery patients (Group B, n=2,637). METHODS: Self-reported health status was assessed using the SF-36 at baseline and after approximately 12 weeks of participation in a contemporary phase 2 CR program. RESULTS: On program exit, improvements (p<0.05 for within group change from baseline) in SF-36 transformed scores were observed, as follows: physical functioning (Group A, 13; Group B, 19); role-physical (Group A, 35; Group B, 41); bodily pain (Group A, 13; Group B 22); general health (Group A, 4; Group B, 3); vitality (Group A, 10; Group B, 12); social functioning (Group A, 17; Group B, 23); role-emotional (Group A, 12; Group B, 16); and mental health (Group A, 6; Group B, 6). With the exception of general health (slightly greater improvement in Group A versus Group B patients) and mental health (no difference between groups), the magnitude of improvement from baseline was significantly greater (p<0.05) for Group B versus Group A patients. CONCLUSION: These data serve to document the magnitude of improvement in self-reported health status in post-myocardial infarction and post-coronary artery bypass graft surgery patients in response to participation in a contemporary phase 2 CR program. The data demonstrate that both groups of patients experience significant improvements in multiple indices of self-reported health status and that the magnitude of improvement differs for certain indices in post-myocardial infarction versus postcoronary artery bypass graft surgery patients.

Introduction: A meta-analysis to evaluate the physiologic changes associated with Cardiac Rehabilitation (CR) in post myocardial infarction (MI) patients was conducted. Hypothesis: CR is a non-pharmacological intervention associated with improved outcomes after MI Methods: We performed an online database search of PubMed, MEDLINE, EMBASE, SCOPUS, COCHRANE, and GOOGLE SCHOLAR (1988 - Present); and reviewed key bibliographies. Studies comparing post MI patients according to CR referral were included. Relative risks with the corresponding 95% confidence intervals (CI) by random effects models of pooled data were calculated. Study quality was assessed using STROBE criteria. Outcomes of interest measured after conclusion of CR, these included resting and maximum heart rate (HR), Peak VO2, ejection fraction (EF), wall motion score index (WMSI), left ventricular end diastolic diameter (LVEDD) Results: Of 147 studies searched, 23 studies met our selection criteria, 19 of which were randomized clinical trials, including 1683 patients (827 referred to CR vs 855 not enrolled in CR). Median age was 58 years. There were no significant difference between the two groups in terms of age, comorbidities, severity, baseline EF or HR. CR patients had significantly lower post-exercise resting HR (RR:-0.72, CI:-0.87 to -0.56; p&lt;0.05), higher EF (RR:0.14, CI:0.04-0.25, p&lt;0.05), lower LVEDD (RR: -0.31, CI:-059,-0.02;p &lt;0.05), lower WMSI (RR:-0.33, CI:-0.62, -0.05; p&lt;0.05), and higher peak VO2 (RR:1.00, CI:0.56 - 1.45; p&lt;0.05) Conclusions: This meta-analysis demonstrates that CR is associated with positive physiologic changes post MI. This may explain the reported improvement of functional status and decreased mortality among patients referred to CR. Further randomized trials may help evaluate the long term benefits of CR

The pharmacologic management of the patient post myocardial infarction (MI) aims to achieve several goals. Chief among these is to prevent subsequent events, which include death, reinfarction, and rehospitalization. Secondary goals include preventing arrhythmias, minimizing left ventricular (LV) remodeling, and preventing progression to heart failure. This review describes practical algorithms for use in the pharmacologic management of the patient post MI based on American Heart Association/American College of Cardiology guidelines. The intensity of drug treatment is determined guided by the degree of LV dysfunction and the presence or absence of ischemia and arrhythmic risk markers. All patients post MI require an angiotensin-converting enzyme (ACE) inhibitor and antiplatelet therapy, usually with aspirin. In individuals who cannot tolerate an ACE inhibitor, an angiotensin receptor blocker (ARB) is an adequate substitute. Numerous studies document the efficacy of ACE inhibitors, which decrease mortality and the risk of heart failure and stroke. Aldosterone blockade is recommended long-term for patients post MI with an LV ejection fraction < or = 40% and either symptomatic heart failure or diabetes. Use of a beta blocker is an important addition to most post-MI drug regimens. Beta blockers decrease mortality and are especially effective in patients with impaired LV function. Among the beta blockers, carvedilol, which also has alpha-adrenergic receptor blocking activity, was found to decrease mortality significantly in patients with low ejection fractions and heart failure. Another drug therapy of value in post-MI treatment is use of calcium-channel blockers. These are restricted to patients with conserved LV function in whom congestion is absent and in whom beta blockers are contraindicated. Current guidelines also recommend that patients post MI with elevated cholesterol levels should be prescribed lipid therapy with a statin at hospital discharge.

Introduction Sudden cardiac death (SCD) in post myocardial infarction (post-MI) patients with a relatively preserved left ventricular ejection fraction (LVEF ≥40%) has 1% annual incidence. In the PRESERVE-EF study, we used a two-step SCD risk stratification approach to detect patients with a relatively preserved left ventricular ejection fraction ≥40% at risk for major arrhythmic events. Seven noninvasive risk factors (NIRFs) were extracted from ambulatory electrocardiography. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS). Inducible patients received an ICD. Purpose The present study examines the performance of machine learning technology for the prediction of the inducible patients in PRESERVE-EF study. Methods After first step screening with NIRFs, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analysed. We used machine learning of NIRFs to predict these inducible high risk patients. We selected as classification method the Nearest Neighbour (NN) algorithm, after experimentation with several classifiers. NN classifies each subject according to the class of the N nearest neighbours. For each subject, we created a vector with the following 7 features: SAECG Late Potentials, Ventricular Premature beats ≥30/hour, Non-sustained Ventricular Tachycardia ≥1 episode (s)/24 hours, Fredericia corrected QT interval ≥45 0ms, SDNN/HRV ≤75 ms, T Wave Alternans ≥65 μV, Combined Deceleration capacity (DC) ≤4.5 ms and Heart Rate Turbulence Onset (To) ≥0% and Heart Rate Turbulence Slope (Ts) ≤2.5 ms. Results The achieved accuracy reached up to 72.2% when N was set to 7. We had totally 144 samples, 41 of which were inducible high risk patients. Results were similar for other values of N. To ensure independence of train and test sets, we employed 10-fold cross validation. Conclusions Inducible on PVS patients in PRESERVE-EF study were predicted with machine learning classification of NIRFs. Funding Acknowledgement Type of funding sources: None.

Purpose: Searching for new biomarkers to predict the progress of coronary artery disease (CAD), we studied the evolution of lipid and inflammatory parameters, along with five mi-RNAs, in plasma of CAD patients under treatment for 1 year. Methods: Subjects were assigned to 5 groups: healthy subjects (C, 10), subjects with risk factors (RF, 10), stable angina (SA, 22), unstable angina (UA, 21) and 1 month post myocardial infarction (MI, 11) patients. Blood was collected at inclusion and after 1 year of standard treatment. We selected five miRNA (miR-92a, miR486a, miR-125a, miR-146a, miR-33a), due to their implication in lipid metabolism, cardiomyocytes and endothelial dysfunction. Lipid parameters were measured in plasma and serum, such as total cholesterol, triglycerides, phospholipids, LDL-C, HDL-C, and oxidative stress markers, such as oxidized LDL, 4-hydroxynonenal (4-HNE), 15(S)-hydroxy-eicosatetraenoic acid, 13(S)-hydroxyoctadecadienoic levels and paraoxonase-1(PON-1) activity. IL-1β, CRP, matrix metalloproteases (MMP-9, MMP-14) and soluble vascular adhesion protein (sVAP-1) were determined as inflammatory markers. The statistical correlation between biochemical and clinical parameters was performed. Results: After 1-year of treatment, our evaluation showed a significant improvement of the plasma lipid profile, decrease of the oxidative (lower plasma 4-HNE levels and increased serum PON1 activity) and inflammatory stress (lower IL-1β levels and MMP-9 activity). Interestingly, IL-1β levels were increased in sera from SA and UA patients under 60 compared to those over 60. Also, MMP-14 levels were increased in UA and decreased in MI sera from patients under 60 compared to those over 60. Levels of sVAP-1 were increased in MI (406.9±72.34) compared to UA (348.29±50.52, p<0,05) patients plasma. Plasma sVAP-1 levels were significantly increased in all diabetic versus non diabetic patients (p<0,05). Circulating miR-486a and miR-92a levels were increased in MI compared to UA sera. All miRs levels were increased in UA patients under 60 compared to those over 60. Conclusions. As a consequence of the standard treatment administered, the lipid profile after 1 year suffered a definite improvement compared to baseline. The decrease of IL-1β levels and MMP-9 activity in all patients' sera after one year treatment suggests that they might be adequate CAD markers. The increased levels of sVAP-1 in diabetic and post myocardial infarction patients indicate that this molecule could be a predictive marker for CAD evolution. The role of miRs as prognostic markers remains still under debate.

Effects of proprotein convertase subtilisin-kexin type 9 inhibitors on inflammatory and hemostatic parameters in post myocardial infarction patients

Comprehensive cardiac rehabilitation aims primarily at improving quality of life, but an effect on morbidity and mortality may also be expected, especially when changes in behaviour and life-style are induced. The value of relaxation therapy and exercise training in post myocardial infarction (MI) patients was investigated. A group of 90 post MI patients were randomly assigned to either exercise training plus individual relaxation and breathing therapy (treatment A), or exercise training only (treatment B). The occurrence of cardiac events, consisting of cardiac death and of readmission to hospital for unstable angina pectoris, coronary artery bypass grafting (CABG) or recurrent infarction, differed significantly for the two treatment groups in the 2-3 years after infarction. Seven out of 42 patients in treatment group A (17%) experienced a cardiac event, in contrast to 17 out of 46 (37%) patients in treatment group B, (P = 0.05, two-tailed). The results suggest that a combination of a behavioural treatment such as relaxation therapy with exercise training is more favourable for the long-term outcome after myocardial infarction than is exercise training alone.

Introduction Available mapping data in post-myocardial infarction patients describe ventricular tachycardia (VT) re-entry circuit characteristics of slow VT, that are typically related to transmural scars. Fast VTs with cycle lengths close to the refractory period may be related to functional re-entry in the scar border zone. Functional re-entry related border zone VTs may be difficult to control by ablation. Purpose The aims of this study are (1) to describe electroanatomical voltage map (EAVM) characteristics in post myocardial infarction (MI) patients with spontaneous and inducible fast VTs and (2) to assess the relation between scar border zone size and ablation outcomes. Methods Consecutive post-MI patients undergoing VT ablation at a tertiary referral center from January 2012 to November 2018 were included. Fast VT was defined as a VT cycle length (VTCL) = ventricular refractory period + max. 30ms. Areas of scar border zone (using 0.5 – 2.1mV/3.0mV cut-offs (according to LV remodeling stage; LVEF&amp;lt;47% and LV end-systolic volume index of &amp;gt;50 ml/m2)) were measured on the EAVM and correlated with clinical outcomes. Results In total, 138 patients were included (86% male; left ventricular ejection fraction 35±10%; 86% remodeled LV). Twenty-three patients (17%) had ≥1 fast VT (mean VTCL 275±52ms) at presentation, mean VTCL of the remaining patients 397±88ms). The median scar border zone size was 27% [IQR 20-38] of the left ventricular endocardial surface. Patients who presented with a spontaneous fast VT had a larger border zone than patients with slower VT (32% [IQR 28 – 41] vs. 25% [IQR 16 – 36], p=0.01). After ablation, 79 (57%) patients remained inducible for any VT, including 59/79 (75%) for a fast VT (median VTCL fast VT 260ms [IQR 236 -280]). Patients who remained inducible for fast VTs had a larger border zone than patients who remained inducible for slower VTs (35% [IQR 27 – 44] vs. 26% [IQR 20 – 36], p&amp;lt;0.001). During a median follow-up of 26 months [IQR 8 – 47], 45 patients (33%) had a VT recurrence (mean VTCL 357±98ms). Patients with a below median (27%) scar border zone area had a lower VT recurrence rate compared to patients with an above median scar border zone area (recurrence rate: 16/66 (24%) vs. 29/72 (40%), p=0.03). Kaplan-Meier survival analysis showed better free VT survival in the below median border zone patients (Log-rank: p&amp;lt;0.05) (Figure 1). Conclusion Patients who present with spontaneous fast VTs or who remain inducible for fast VTs after ablation have larger scar border zones during EAVM compared to patients with presenting or remaining slower VTs. A larger border zone appeared to be associated with higher VT-recurrence rates. The scar border zone may play an important role as VT substrate for (fast) VTs and may not be easily targeted by current ablation techniques.VT-free survival stratified by median BZ

Sudden cardiac death (SCD) remains a major public health issue with an estimated annual inci‐ dence of 300,000 cases per year. The ACC/AHA/ESC 2006 guidelines define SCD as “death from an unexpected circulatory arrest, usually due to a cardiac arrhythmia occurring within an hour of the onset of symptoms” [1]. Trials on traditional antiarrhythmic drugs have failed to show any mortality benefit even when compared to placebo or implantable cardiovertor defibrilla‐ tors (ICDs) [2]. Most of the patients experiencing sudden cardiac arrest have left ventricular ejection fraction (LVEF) > 50%, with the majority of these patients having a history of coronary artery disease (CAD). Majority of Sudden Cardiac Arrests (85-90%) are the first arrhythmic event a patient experiences[3].Beta blocker therapy, Angiotensin enzymes inhibitors (ACE-I) as well as aldosterone antagonists have been shown to decrease the risk of sudden cardiac death especially in post myocardial infarction (MI) patients and in patients with congestive heart fail‐ ure. This chapter will review the data on the effects of traditional heart failure medications, es‐ pecially beta blockers, Renin Angiotensin system blockers, as well as Statin therapy on sudden cardiac death in post MI patients and in patients with cardiomyopathy.

Traditional Heart Failure Medications and Sudden Cardiac Death Prevention

Background: ACC/AHA guidelines strongly recommend the use of aspirin, beta blockers, clopidogrel, statin, and angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) in post myocardial infarction (MI) patients. Reductions in mortality have been demonstrated with consistent administration of recommended therapies. Patients who discontinue taking evidence-based medications are at increased mortality risk. The purpose of this study was to identify gender and age based differences in drug therapies at discharge in post MI patients at a tertiary care teaching hospital. Methods: We retrospectively analyzed data of 610 consecutive patients admitted with MI from 2006 to 2007. The use of appropriate discharge medications was compared using chi-square test. Results: There were 371 males (60.8%) with mean age 65.4 ±13 years and 239 females (39.2%) with mean age 73 ±12 years. Medications Male (%) Female (%) OR (CI) p value Aspirin 97.9 93.2 3.4 (1.3-8.5) 0.006 Clopidogrel 77.6 63.6 1.98(1.4-2.87) &lt;0.001 Beta blocker 94.6 84.4 3.2 (1.75-5.9) &lt;0.001 Statin 88 79 1.9 (1.2-3.1) 0.006 ACEI/ARB 70 58.5 1.66(1.15-2.3) 0.006 Clopidogrel use was 59% and 84.4% in patients greater than 70 years and less than 70 years respectively (OR= 0.26, CI 0.18-0.39, p = &lt;0.001). There was no difference in use of other medications by an age cut off of 70 years. Conclusions: In an era of evidence-based guidelines and quality improvement initiatives, there is still under utilization of recommended medications in women even though they receive same treatment benefit. Elderly patients in spite of being at high risk for recurrent events were less likely to be discharged with dual antiplatelet therapy.

QT dispersion (QTd) has not proven to be a useful marker derived from the 12-lead electrocardiogram (ECG) for stratification of patients at risk for sudden cardiac death. To overcome its methodological shortcomings, novel ECG variables of T wave morphology have been proposed. The total cosine R-to-T (TCRT), T wave morphology dispersion, T wave loop dispersion, normalized T wave loop area, as well as absolute and relative T wave residuum evaluating non-dipolar ECG signal contents were evaluated in two clinical studies involving post myocardial infarction (MI) patients and US veterans with cardiovascular disease. In 280 post MI patients with 27 events over a mean follow-up of 32 months, TCRT and T wave loop dispersion were independent predictors of mortality. In 813 male US veterans with cardiovascular disease the absolute and relative T wave residua were independent predictors of patient risk during a long-term follow-up of more than 10 years. On Cox regression analysis, age, presence of left ventricular hypertrophy (LVH) and left ventricular ejection fraction (LVEF) were also predictors of survival. The latter study in US veterans therefore was the first to demonstrate that a novel parameter characterizing heterogeneity of ventricular repolarization within the 12-lead surface ECG permits risk stratification in patients with cardiovascular disease. All of the ECG variables are easily accessible from digital 12-lead surface ECG recordings using custom computer programs. They may prove useful to identify risk patients that benefit from the implantable cardioverter-defibrillator (ICD).