Statin Therapy and Intensity: Prognosis in Patients with Myocardial Injury.

BACKGROUND: No guideline-directed pharmacological therapy has been established for patients with myocardial injury without type 1 myocardial infarction. We investigated the impact of statin treatment in patients with myocardial injury. METHODS: Patients with myocardial injury (nonischemic acute and chronic myocardial injury), type 2 myocardial infarction, and type 1 myocardial infarction with at least 1 emergency department visit for chest pain from 2011 to 2014 were included. Dispensed prescriptions of all types of statins with dosage within 180 days from the index visit were collected. In total, 2054 patients were divided into 3 groups: 1) acute myocardial injury (type 2 myocardial infarction, acute nonischemic myocardial injury), 2) chronic myocardial injury, and 3) type 1 myocardial infarction. We estimated the adjusted hazard ratio with 95% confidence interval for death with low- (reference), moderate-, and high-intensity statin therapy. RESULTS: The mean follow-up was 4.2 ± 1.8 years. Only 13% of patients with acute and chronic myocardial injury and 30% with type 1 myocardial infarction were treated with high-intensity statins. Adjusted mortality rates were higher in patients with acute and chronic myocardial injury than in those with type 1 myocardial infarction across all statin intensity categories. In patients with type 1 myocardial infarction, the adjusted mortality risk was 20% (hazard ratio, 0.80; 95% confidence interval, 0.36-1.77) lower in patients with high-intensity therapy. Point estimates in the adjusted models indicated similar associations between statin intensity and mortality risk in patients with acute and chronic myocardial injury. CONCLUSION: Patients with myocardial injury may benefit from high-intensity statin treatment, but the associations were not statistically significant when adjusting for confounders.

Plasma Level of Elabela in Patients with Coronary Heart Disease and Its Correlation with the Disease Classification.

This study aimed to evaluate the concentration of plasma elabela (ELA) in patients with coronary heart disease (CHD) and its correlation with the disease classification.We enrolled 238 patients diagnosed by coronary angiography as CHD and 86 controls. The CHD group was divided into three subgroups: stable angina (SA), unstable angina (UAP), and acute myocardial infarction (AMI). The plasma levels of ELA were measured in all participants and compared among different groups. The relationship between ELA and CHD classification was analyzed.ELA levels were markedly higher by 10.71% in patients with CHD than in controls (P < 0.05). The concentration of ELA in UAP and AMI subgroups were higher than in controls and SA subgroup. The former difference was significant (P < 0.05), but the latter was not. In addition, the ELA concentration was not correlated with SYNTAX score, left ventricular ejection fraction, and other biochemical variables.The newfound hormone, ELA, significantly increased in patients with UAP and AMI. There is a tendency that ELA levels might be correlated with CHD classification, but not with lesion severity. ELA may play a role in acute coronary syndrome.

Machine learning-based classification and diagnosis of clinical cardiomyopathies.

Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) are two common types of cardiomyopathies leading to heart failure. Accurate diagnostic classification of different types of cardiomyopathies is critical for precision medicine in clinical practice. In this study, we hypothesized that machine learning (ML) can be used as a novel diagnostic approach to analyze cardiac transcriptomic data for classifying clinical cardiomyopathies. RNA-Seq data of human left ventricle tissues were collected from 41 DCM patients, 47 ICM patients, and 49 nonfailure controls (NF) and tested using five ML algorithms: support vector machine with radial kernel (svmRadial), neural networks with principal component analysis (pcaNNet), decision tree (DT), elastic net (ENet), and random forest (RF). Initial ML classifications achieved ~93% accuracy (svmRadial) for NF vs. DCM, ~82% accuracy (RF) for NF vs. ICM, and ~80% accuracy (ENet and svmRadial) for DCM vs. ICM. Next, 50 highly contributing genes (HCGs) for classifying NF and DCM, 68 HCGs for classifying NF and ICM, and 59 HCGs for classifying DCM and ICM were selected for retraining ML models. Impressively, the retrained models achieved ~90% accuracy (RF) for NF vs. DCM, ~90% accuracy (pcaNNet) for NF vs. ICM, and ~85% accuracy (pcaNNet and RF) for DCM vs. ICM. Pathway analyses further confirmed the involvement of those selected HCGs in cardiac dysfunctions such as cardiomyopathies, cardiac hypertrophies, and fibrosis. Overall, our study demonstrates the promising potential of using artificial intelligence via ML modeling as a novel approach to achieve a greater level of precision in diagnosing different types of cardiomyopathies.

Valor pronóstico de la cardiorresonancia magnética de estrés en pacientes ancianos / Prognostic role of stress cardiac magnetic resonance in the elderly

INTRODUCCIÓN Y OBJETIVOS: Diferentes estudios han demostrado el valor diagnóstico y pronóstico de la resonancia magnética cardiaca (RMC) de estrés en pacientes con cardiopatía isquémica. No obstante, la evidencia en ancianos es escasa, en parte por las limitaciones de las técnicas diagnósticas disponibles para esta población. El objetivo de este estudio es evaluar la utilidad de la RMC de estrés en pacientes ancianos. MÉTODOS: Se estudió de manera prospectiva a los pacientes remitidos a una RMC de estrés para descartar isquemia miocárdica. Se consideró paciente anciano a los mayores de 70 años. El estudio de RMC de estrés se realizó conforme a los protocolos internacionales. La gravedad de la hipoperfusión se clasificó en función de los segmentos afectados: ligera (1-2 segmentos), moderada (3-4 segmentos) o grave (> 4 segmentos). Se analizó la aparición de eventos mayores durante el seguimiento (muerte, síndrome coronario agudo o revascularización). La supervivencia se analizó con el método de Kaplan-Meier y un modelo de regresión multivariante de Cox. RESULTADOS: De la cohorte inicial de 333 pacientes, 110 eran mayores de 70 años. En el 40,9% de estos, la RMC de estrés fue positiva para isquemia. La mediana de seguimiento fue de 26 [18-37] meses. En los pacientes ancianos se registraron 35 eventos: 15 fallecimientos, 10 síndromes coronarios agudos y 10 revascularizaciones. Los pacientes con isquemia moderada o grave tenían mayor riesgo de eventos ajustado por edad, sexo y riesgo cardiovascular (HR=3,53; IC95%, 1,41-8,79; p = 0,01). CONCLUSIONES: La presencia de hipoperfusión moderada o grave detectada mediante RMC de estrés predice de manera significativa la aparición de eventos en mayores de 70 años, sin que aparezcan efectos adversos relevantes

INTRODUCTION AND OBJECTIVES: Several trials have tested the diagnostic and prognostic value of stress cardiac magnetic resonance (CMR) in ischemic heart disease. However, scientific evidence is lacking in the older population, and the available techniques have limitations in this population. The aim of this study was to evaluate the usefulness of stress CMR in the elderly. METHODS: We prospectively studied consecutive patients referred for stress CMR to rule out myocardial ischemia. The cutoff age for the elderly population was 70 years. Stress CMR study was performed according to standardized international protocols. Hypoperfusion severity was classified according to the number of affected segments: mild (1-2 segments), moderate (3-4 segments), or severe (> 4 segments). We analyzed the occurrence of major events during follow-up (death, acute coronary syndrome, or revascularization). Survival was studied with the Kaplan-Meier method and multivariate Cox regression models. RESULTS: Of an initial cohort of 333 patients, 110 were older than 70 years. In 40.9% patients, stress CMR was positive for ischemia. The median follow-up was 26 [18-37] months. In elderly patients there were 35 events (15 deaths, 10 acute coronary syndromes, and 10 revascularizations). Patients with moderate or severe ischemia were at a higher risk of events, adjusted for age, sex, and cardiovascular risk (HR, 3.53 [95%CI, 1.41-8.79]; P=.01). CONCLUSIONS: Moderate to severe perfusion defects in stress CMR strongly predict cardiovascular events in people older than 70 years, without relevant adverse effects

Ischemia in patients with no obstructive coronary artery disease: classification, diagnosis and treatment of coronary microvascular dysfunction.

Patients with coronary microvascular dysfunction represent a widespread population, and despite the good prognosis, many of them, because of the angina symptoms, have a poor quality of life with strong limitations in their daily activities. In 2017, a new classification of microvascular dysfunction as well as a new definition of ischemia in patients with no obstructive coronary artery disease became available. This new definition improves Kemp's initial work, where cardiac X syndrome was initially described. This work summarizes the last updates on the subject with particular attention to the new classification of microvascular dysfunction, with particular attention to microvascular and vasospastic angina definition and diagnostic criteria.

Prognostic role of stress cardiac magnetic resonance in the elderly.

INTRODUCTION AND OBJECTIVES: Several trials have tested the diagnostic and prognostic value of stress cardiac magnetic resonance (CMR) in ischemic heart disease. However, scientific evidence is lacking in the older population, and the available techniques have limitations in this population. The aim of this study was to evaluate the usefulness of stress CMR in the elderly. METHODS: We prospectively studied consecutive patients referred for stress CMR to rule out myocardial ischemia. The cutoff age for the elderly population was 70 years. Stress CMR study was performed according to standardized international protocols. Hypoperfusion severity was classified according to the number of affected segments: mild (1-2 segments), moderate (3-4 segments), or severe (> 4 segments). We analyzed the occurrence of major events during follow-up (death, acute coronary syndrome, or revascularization). Survival was studied with the Kaplan-Meier method and multivariate Cox regression models. RESULTS: Of an initial cohort of 333 patients, 110 were older than 70 years. In 40.9% patients, stress CMR was positive for ischemia. The median follow-up was 26 [18-37] months. In elderly patients there were 35 events (15 deaths, 10 acute coronary syndromes, and 10 revascularizations). Patients with moderate or severe ischemia were at a higher risk of events, adjusted for age, sex, and cardiovascular risk (HR, 3.53 [95%CI, 1.41-8.79]; P=.01). CONCLUSIONS: Moderate to severe perfusion defects in stress CMR strongly predict cardiovascular events in people older than 70 years, without relevant adverse effects.

Tree-Based Analysis.

Tree-based methods have become one of the most flexible, intuitive, and powerful data analytic tools for exploring complex data structures. Tree-based methods provide a natural framework for creating patient subgroups for risk classification. In this article, we review methodological and practical aspects of tree-based methods, with a focus on diagnostic classification (binary outcome) and prognostication (censored survival outcome). Creating an ensemble of trees improves prediction accuracy and addresses instability in a single tree. Ensemble methods are described that rely on resampling from the original data. Finally, we present methods to identify a representative tree from the ensemble that can be used for clinical decision-making. The methods are illustrated using data on ischemic heart disease classification, and data from the SPRINT trial (Systolic Blood Pressure Intervention Trial) on adverse events in patients with high blood pressure.

Outcome of all-comers with STEMI based on the grade of ischemia in the presenting ECG.

BACKGROUND: Grade 3 ischemia (G3I) in the 12­lead electrocardiogram (ECG) predicts poor outcome in patients with ST-elevation myocardial infarction (STEMI). The outcome of G3I in "real-life" patient cohorts is unclear. METHODS: The aim of the study was to establish the prognostic significance of grade 2 ischemia (G2I), G3I and the STEMI patients excluded from ischemia grading (No grade of ischemia, NG) in a real-life patient population. We assessed in-hospital, 30-day and 1-year mortality as well as other endpoints. RESULTS: The NG patients had more comorbidities and longer treatment delays than the two other groups. Short-term and 1-year mortality were highest in patients with NG and lowest in patients with G2I. Maximum troponin level was highest in G3I, followed by NG and G2I. In logistic regression multivariable analysis, NG was independently associated with 1-year mortality. CONCLUSIONS: NG predicted poor outcome in STEMI patients. G2I predicted relatively favorable outcome.

Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction.

BACKGROUND: During primary percutaneous coronary intervention (PCI), a concurrent chronic total occlusion (CTO) is found in 10% of patients with ST-elevation myocardial infarction (STEMI). Long-term benefits of CTO-PCI have been suggested; however, randomised data are lacking. Our aim was to determine mid-term and long-term clinical outcome of CTO-PCI versus CTO-No PCI in patients with STEMI with a concurrent CTO. METHODS: The Evaluating Xience and left ventricular function in PCI on occlusiOns afteR STEMI (EXPLORE) was a multicentre randomised trial that included 302 patients with STEMI after successful primary PCI with a concurrent CTO. Patients were randomised to either CTO-PCI or CTO-No PCI. The primary end point of the current study was occurrence of major adverse cardiac events (MACE): cardiac death, coronary artery bypass grafting and MI. Other end points were 1-year left ventricular function (LVF); LV-ejection fraction and LV end-diastolic volume and angina status. RESULTS: The median long-term follow-up was 3.9 (2.1-5.0) years. MACE was not significantly different between both arms (13.5% vs 12.3%, HR 1.03, 95% CI 0.54 to 1.98; P=0.93). Cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality (12.9% vs 6.2%, HR 2.07, 95% CI 0.84 to 5.14; P=0.11). One-year LVF did not differ between both arms. However, there were more patients with freedom of angina in the CTO-PCI arm at 1 year (94% vs 87%, P=0.03). CONCLUSIONS: In this randomised trial involving patients with STEMI with a concurrent CTO, CTO-PCI was not associated with a reduction in long-term MACE compared to CTO-No PCI. One-year LVF was comparable between both treatment arms. The finding that there were more patients with freedom of angina after CTO-PCI at 1-year follow-up needs further investigation. CLINICAL TRIAL REGISTRATION: EXPLORE trial number NTR1108 www.trialregister.nl.

Treatment and outcomes of type 2 myocardial infarction and myocardial injury compared with type 1 myocardial infarction.

BACKGROUND: Type 2 myocardial infarction (MI) is defined by a rise and fall of cardiac biomarkers and evidence of ischemia without unstable coronary artery disease (CAD) because of a mismatch in myocardial oxygen supply and demand. Myocardial injury is similar but does not fulfill the clinical criteria for MI. There is uncertainty in terms of the clinical characteristics, management, and outcomes of type 2 MI and myocardial injury in comparison with type 1 MI. PATIENTS AND METHODS: Patients admitted to a Veterans Affairs tertiary care hospital with a rise and fall in cardiac troponin were identified. MI and injury subtypes, presentation, management, and outcomes were determined. RESULTS: Type 1 MI, type 2 MI, and myocardial injury occurred in 137, 146, and 175 patients, respectively. Patients with type 2 MI were older (P=0.02), had lower peak cardiac troponin (P<0.001), and were less likely to receive aspirin and statin at discharge (P<0.001) than type 1 MI survivors. All-cause mortality (median follow-up: 1.8 years) was not different between patient groups (type 1 MI mortality: 29.9%, type 2 MI: 30.8%, myocardial injury: 29.7%; log rank P=0.94). A significant proportion of deaths were attributed to cardiovascular causes in all subgroups (type 1 MI: 34.1%, type 2 MI: 17.8%, myocardial injury: 30.8%). CONCLUSION: Patients with type 2 MI and myocardial injury were less likely to receive medical therapy for CAD than those with type 1 MI. No differences in all-cause mortality among MI subtypes were observed. Additional studies to determine optimal medical therapy and risk stratification strategies for these high-risk populations are warranted.

Takotsubo is not a cardiomyopathy.

Unraveling the mechanisms underlying Takotsubo (TTS) leads to question the current inclusion of the condition within the spectrum of cardiomyopathies. Indeed, the clinical presentation and pathophysiology of TTS clearly differ from cardiomyopathies, i.e. diseases of heart muscle unexplained by abnormal loading conditions or coronary artery disease, which cannot recover spontaneously and may cause sudden death often in minimally symptomatic individuals or result in a gradual deterioration in ventricular function and end-stage heart failure. Furthermore, the term 'cardiomyopathy' can no longer be applied when functional or morphologic abnormalities of the coronary arteries leading to acute myocardial ischemia are deemed responsible for left ventricular (LV) systolic dysfunction. After 27years of investigation, time has come to recognize that patients with TTS do suffer from severe myocardial ischemia and fulfill all criteria of acute coronary syndromes, i.e. acute chest pain, typical electrocardiographic changes, cardiac troponin rise, as well as LV wall motion abnormalities. Accordingly, we propose that TTS should be labeled as an acute 'syndrome' to be included more appropriately within the spectrum of ischemic heart disease. With regard to the term 'stress', it may imply that the catecholamine surge is essential to produce the typical transient myocardial injury. Thus, the terminology 'Takotsubo (stress) syndrome' would more accurately reflect recent advances in the pathophysiology.

Echocardiography and Electrocardiography Variables Correlate With the New York Heart Association classification: An Observational Study of Ischemic Cardiomyopathy Patients.

The aim of our study was to determine whether combinations of ultrasound echocardiography (UCG) and electrocardiography (EKG) parameters correlated with the functional status of ischemic cardiomyopathy (ICM) patients according to the New York Heart Association (NYHA) classification system.We assessed 536 elderly Chinese ICM patients according to the NYHA criteria, which included 196 patients with type 2 diabetes mellitus (T2DM). All of the patients underwent UCG. Transmural dispersion of ventricular repolarization was examined using EKG. Cumulative odds logistic regression was performed to evaluate associations between NYHA class and the demographic, clinical, UCG, and EKG variables based on the odds ratio (OR) and 95% confidence interval (CI). A Pearson analysis was also performed to examine correlations between the NYHA classification and the UCG and EKG variables.Based on the NYHA assessment, 140, 147, 138, and 111 patients were identified as class I, II, III and IV, respectively. A comparison of UCG and EKG variables based on T2DM status showed that CO and Tp-e differed significantly between all NYHA classes (P < .05 for all), with values of each increasing with increasing NYHA class regardless of T2DM status. Multivariate logistic regression analysis showed that the disease course (OR: 1.30; 95% CI: 1.20-1.40), heart rate (OR: 1.16; 95% CI: 1.12-1.21), T wave peak to endpoint (Tp-e; OR: 1.22; 95% CI: 1.18-1.27), dispersion of the QT interval (OR: 0.98; 95% CI: 0.95-1.22), left ventricular fractional shortening (OR: 0.82; 95% CI: 0.78-0.87), cardiac output (CO; OR: 5.58; 95% CI: 3.08-10.13) were significantly associated with the NYHA class (P < .0001 for all). A Pearson correlation analysis showed that Tp-e (r = 0.75982, P < .0001), CO (r = 0.56072, P < .0001), and stroke volume (r = -0.14839, P = .0006) significantly correlated with the NYHA class.An index consisting of Tp-e and CO will be useful for corroborating the results of the NYHA assessment of ICM patients.

Is the Mortality Trend of Ischemic Heart Disease by the GBD2013 Study in China Real?

To determine the reason for the different mortality trends of ischemic heart disease (IHD) for China between Global Burden of Disease (GBD) 2010 and GBD2013, and to improve garbage code (GC) redistribution. All data were obtained from the disease surveillance points system, and two proportions for assigning chronic pulmonary heart disease (PHD) as GC to IHD were from GBD2010 and GBD2013, which were different for years before 2004. By using the GBD2013 approach, the age-standard mortality rate (ASMR) increased by 100.21% in 1991, 44.81% in 1996, and 42.47% in 2000 in comparison with the GBD2010 approach. The different methods of chronic PHD redistribution impacted the trend of IHD mortality, which elevated it in the earlier 1990s by using the GBD2013 approach. Thus, improving the redistribution of GC as a key step in mortality statistics is important.

Taxonomy of segmental myocardial systolic dysfunction.

The terms used to describe different states of myocardial health and disease are poorly defined. Imprecision and inconsistency in nomenclature can lead to difficulty in interpreting and applying trial outcomes to clinical practice. In particular, the terms 'viable' and 'hibernating' are commonly applied interchangeably and incorrectly to myocardium that exhibits chronic contractile dysfunction in patients with ischaemic heart disease. The range of inherent differences amongst imaging modalities used to define myocardial health and disease add further challenges to consistent definitions. The results of several large trials have led to renewed discussion about the classification of dysfunctional myocardial segments. This article aims to describe the diverse myocardial pathologies that may affect the myocardium in ischaemic heart disease and cardiomyopathy, and how they may be assessed with non-invasive imaging techniques in order to provide a taxonomy of myocardial dysfunction.

Ischemic QRS prolongation as a biomarker of severe myocardial ischemia.

BACKGROUND: Previous studies have shown that QRS prolongation is a sign of depressed collateral flow and increased rate of myocardial cell death during coronary occlusion. The aims of this study were to evaluate ischemic QRS prolongation as a biomarker of severe ischemia by establishing the relationship between prolongation and collateral flow experimentally in a dog model, and test if the same pattern of ischemic QRS prolongation occurs in man. METHODS: Degree of ischemic QRS prolongation was measured using a novel method in dogs (n=23) and patients (n=52) during coronary occlusion for 5min. Collateral arterial flow was assessed in the dogs. RESULTS: There was a significant correlation between QRS prolongation and collateral flow in dogs (r=0.61, p=0.008). Magnitude and temporal evolution of prolongation during ischemia were similar for dogs and humans (p=0.202 and p=0.911). CONCLUSION: Quantification of ischemic QRS prolongation could potentially be used as a biomarker for severe myocardial ischemia.

Disturbed coronary hemodynamics in vessels with intermediate stenoses evaluated with fractional flow reserve: a combined analysis of epicardial and microcirculatory involvement in ischemic heart disease.

BACKGROUND: In chronic ischemic heart disease, focal stenosis, diffuse atherosclerotic narrowings, and microcirculatory dysfunction (MCD) contribute to limit myocardial flow. The prevalence of these ischemic heart disease levels in fractional flow reserve (FFR) interrogated vessels remains largely unknown. METHODS AND RESULTS: Using intracoronary measurements, 91 coronaries (78 patients) with intermediate stenoses were classified in 4 FFR and coronary flow reserve (CFR) agreement groups, using FFR>0.80 and CFR<2 as cutoffs. Index of microcirculatory resistance (IMR) and atherosclerotic burden (Gensini score) were also assessed. MCD was assumed when IMR≥29.1 (75(th) percentile). Fifty-four (59.3%) vessels had normal FFR, from which only 20 (37%) presented both normal CFR and IMR. Among vessels with FFR>0.80, most (63%) presented disturbed hemodynamics: abnormal CFR in 28 (52%) and MCD in 18 (33%). Vessels with FFR>0.80 presented higher IMR [adjusted mean 27.6 (95% confidence interval, 23.4-31.8)] than those with FFR≤0.80 [17.3 (95% confidence interval, 13.0-21.7), p=0.001]. Atherosclerotic burden was inversely correlated with CFR (r=-0.207, P=0.055), and in vessels with FFR>0.80 and CFR<2 (n=28, 39%), IMR had a wide dispersion (7-72.7 U), suggesting a combination of diffuse atherosclerotic narrowings and MCD. Vessels with FFR≤0.80 and normal CFR presented the lowest IMR, suggesting a preserved microcirculation. CONCLUSIONS: A substantial number of coronary arteries with stenoses showing an FFR>0.80 present disturbed hemodynamics. Integration of FFR, CFR, and IMR supports the existence of differentiated patterns of ischemic heart disease that combine focal and diffuse coronary narrowings with variable degrees of MCD.

Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link!

In the current pathophysiological model of chronic ischemic heart disease (IHD), myocardial ischemia and exertional angina are caused by obstructive atherosclerotic plaque, and the clinical management of IHD is centered on the identification and removal of the stenosis. Although this approach has been in place for years, several lines of evidence, including poor prognostic impact, suggest that this direct relationship may present an oversimplified view of IHD. Indeed, a large number of studies have found that IHD can occur in the presence or absence of obstructive coronary artery disease and that atherosclerosis is just 1 element in a complex multifactorial pathophysiological process that includes inflammation, microvascular coronary dysfunction, endothelial dysfunction, thrombosis, and angiogenesis. Furthermore, the high recurrence rates underscore the fact that removing stenosis in patients with stable IHD does not address the underlying pathological mechanisms that lead to the progression of nonculprit lesions. The model proposed herein shifts the focus away from obstructive epicardial coronary atherosclerosis and centers it on the microvasculature and myocardial cell where the ischemia is taking place. If the myocardial cell is placed at the center of the model, all the potential pathological inputs can be considered, and strategies that protect the cardiomyocytes from ischemic damage, regardless of the causative mechanism, can be developed.