SASSCAIA Trial Showed No Difference Between Intensified Prasugrel-Based and Standard Clopidogrel-Based Loading Strategies in Terms of Safety and Efficacy in Patients Undergoing Elective Percutaneous Coronary Intervention

A recent study by Dr. Julinda Mehilli, M.D., published in Circulation journal, has shown that in patients undergoing elective percutaneous coronary intervention (PCI), pretreatment strategy with the intensified prasugrel loading does not differ from standard clopidogrel loading dose in terms of Safety and Efficacy. According to the trial, both strategies can be safely applied among patients undergoing elective PCI.
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Post Hoc Analysis of Randomized SCOT-HEART Trial: Coronary Computed Tomography Is More Strongly Associated With 5-Year Coronary Events Compared With Exercise Electrocardiography

The post hoc analysis of the SCOT-HEART trial by Dr. Adamson MBChB, Ph.D. published in JAMA Cardiology showed that abnormal results of exercise electrocardiography (ECG) were strongly associated with coronary revascularization and increased risk of mortality from coronary heart disease. However, coronary computed tomography (CT) angiography was a more accurate predictor of 5-year coronary events compared with exercise ECG alone. Continue reading

Retrospective Population-Based Cohort Study Showed Increased Mortality of Cardiac Arrest Patients With Non-shockable Rhythm After Application of Targeted Temperature Management

A recent study by Dr. Khan and his colleagues, published in the American Heart Journal, has shown that the application of post-resuscitation targeted temperature management (TTM) or hypothermia protocol was associated with increased mortality in patients with non-shockable associated sudden cardiac arrest (SCA). Additionally, TTM utilization was recognized as an independent predictor of mortality in this specific group after multivariate regression analysis. Continue reading

A Population-Based Study Showed No Association Between COVID-19-Induced In-Hospital Death and Angiotensin-Converting–Enzyme Inhibitors and Angiotensin-Receptor Blockers Use

A recent study by Dr. Mehra, published in the New England Journal of Medicine, disapproved of the previously concerning idea regarding the potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in the clinical context of Coronavirus disease 2019 (Covid-19). This study also demonstrated that Covid-19 may disproportionately affect individuals with cardiovascular disorders.
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E3 Trial: Nicotine E-Cigarettes With Individual Counseling Is More Effective Than Individual Counseling in Smoking Cessation

Dr. Mark J. Eisenberg and his colleagues presented the interim results of the E3 trial to the American College of Cardiology 2020 Meeting. The study was also published in the CJC open journal. According to the E3 trial, the most efficacious way for smoking cessation is nicotine e-cigarettes (ECs) with counseling followed by non-nicotine ECs with individual counseling and individual counseling alone.

Given the clear health benefits of smoking cessation and the increasing desire of smokers for adopting e-cigarettes as a way of quitting smoking, it sounds reasonable to evaluate the efficacy of these agents in smoking abstinence. However, the increasing number of e-cigarettes-associated lung injuries has questioned the safety of these products. The E3 trial aimed at evaluating the efficacy and safety of e-cigarettes for smoking cessation in the general population.

The E3 trial, a multi-center randomized controlled trial, recruited participants motivated for smoking cessation. Individuals with severe diseases and a prognosis of less than a year, a current or recent history of cancer, a current or recent history of drug abuse or a recent history of cardiovascular or cerebrovascular disease, a history of psychiatric disorders and those using e-cigarettes or other medications for smoking cessation were excluded from the study. This resulted in 376 participants who were randomized into three management arms: nicotine ECs, non-nicotine ECs, or no e-cigarettes.  All of them received individual counseling. Treatment allocation for ECs groups was double-blind. The treatment period was done for 12 weeks and individuals were followed for 52 weeks. Follow-up sessions were performed via phone interview (4 sessions) as well as in-person clinic visits (4 sessions). The primary endpoint was the comparison of nicotine-ECs with individual counseling in terms of biochemically-validated point-prevalence smoking abstinence at 12 weeks. The secondary endpoints included the evaluation of ECs efficacy in terms of continuous smoking abstinence and reduction in daily cigarette use as well as ECs safety profile.

In an interview with Dr. C. Michael Gibson, Dr. Mark J. Eisenberg, one of the investigators in the study, discussed the interim results of the study. Point-prevalence abstinence was higher for those who were treated with nicotine-ECs and counseling compared to those who only received counseling (22% versus 9%). In terms of safety, one of the individuals in nicotine-ECs developed COPD exacerbation, and 5 individuals in the non-nicotine ECs group also developed a variety of side effects including epistaxis and chest pain. The E3 trial is going to follow the patients for up to 1 year and the results of this study will be updated. This study will provide health care professionals, and smokers with important information regarding the efficacy and safety of e-cigarettes for smoking cessation.

Click here to listen to the discussion between Dr. C. Michael Gibson and Dr. Eisenberg.

Click here to view the study slides.

Long-Term Follow-Up of the REDUCE-MVI Trial Showed the Superiority of Ticagrelor Over Prasugrel in Maintenance Therapy of Patients With ST-Segment-Elevation Myocardial Infarction

A recent study by Dr. van der Hoeven, published in the Journal of American Heart Association, has shown the superiority of ticagrelor over prasugrel in patients presenting with ST-segment-elevation myocardial infarction (STEMI). According to the author, ticagrelor has a higher efficacy in platelet inhibition as well as in improving endothelial function when compared with prasugrel. Continue reading

Study Shows Myocardial Perfusion Mapping Using Artificial Intelligence Quantification of Cardiovascular Magnetic Resonance Imaging Provides Prognostic Information in Patients With Suspected Coronary Artery Disease Above Traditional Cardiovascular Risk Factors

A recent study by Dr. Knott, published in Circulation, have shown the prognostic value of measuring myocardial blood flow (MBF) using artificial intelligence quantification of cardiovascular magnetic resonance (CMR) perfusion mapping in cardiovascular outcomes. According to this study, both MBF and myocardial perfusion reserve (MPR) were associated with death and major adverse cardiovascular events (MACE) independently of other clinical risk markers. Using this technique, quantitative analysis of myocardial perfusion for clinical use is now available. Continue reading

Cohort Study Showed a Large Number of Patients Receiving Anticancer Therapy Demonstrate Myocardial Injury or Left Ventricular Dysfunction, With Only Few Showing Severe Cardiotoxicity

A recent study by Dr. Lopez-Sendon, published in European Heart Journal, showed that cardiotoxicity in the form of left ventricular dysfunction or myocardial injury affects a large portion of patients receiving high-risk anticancer therapy with only severe form strongly associated with all-cause mortality.

Cardiotoxicity has been known as one of the major side effects of anti-cancer therapy that may present with left ventricular dysfunction and heart failure. Given that the early recognition and treatment of these side effects have been associated with a higher recovery rate, a united diagnostic and management guideline seems necessary.

The CARDIOTOX (CARDIOvascular TOXicity induced by cancer-related therapies) registry has been established to determine the prevalence of cardiotoxicity markers as well as their association with guideline-based heart failure criteria and treatment in patients receiving chemotherapeutic agents. To achieve this purpose, a total of 865 patients receiving anticancer regimens associated with moderate to high cardiotoxicity were selected and followed for a median of 24 months. Clinical data, blood samples, and echocardiographic features were collected before the initiation of anticancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years afterward. Patients with past or current history of heart failure or reduced left ventricular ejection fraction (< 40%) and those with a history of previous cancer therapy including chemotherapy and radiation therapy were excluded from the study. Cardiotoxicity was defined as any new deterioration from the baseline of myocardial/ventricular function during follow-up periods. Cardiotoxicity was also sub-classified into four stages depending on the worst myocardial dysfunction/injury observed in the follow-up period. Myocardial dysfunction/injury stages include the following: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥ 50%; moderate, LVD with LVEF 40–49%; and severe, LVD with LVEF ≤ 40% or symptomatic heart failure.

The study indicated a high incidence (37.5%) of ventricular dysfunction among the patients, of whom only 3.1% were classified as having severe dysfunction and the majority have been classified as mild (31.6%). All-cause mortality was also observed to be higher among those with severe cardiotoxicity than other groups. According to the author, the relatively low prevalence of severe cardiotoxicity in the study population was due to the exclusion of patients with a previous history of cardiac dysfunction and the improvement in the follow-up of the cancer patients in the context of cardio-oncology service. Severe cardiotoxicity has also been associated with a 10-fold increase in total mortality compared to a less severe form of cardiotoxicity. A classification of cardiotoxicity using current heart failure guidelines is also proposed by the authors for future studies. This study acknowledged the critical role of comprehensive monitoring and follow-up for the development of cardiovascular symptoms and left ventricular dysfunction in patients receiving chemotherapeutic agents with potential cardiotoxicity.

Limitations that are worthy of mentioning include the inclusion of patients with some degree of abnormality in biomarkers and echocardiographic findings at baseline. Secondly, the prevalence of myocardial damage may be underestimated due to a number of missing visits or incomplete data collection during the follow-up period. Future research is warranted to approve the relationship of different stages of cardiotoxicity with clinical outcomes.

Trial Showed Implementation of High Sensitivity Cardiac Troponin Assays and Universal Definition of Myocardial Infarction Recommendations in Patients with Suspected Acute Coronary Syndrome Increased Diagnosis Rate Without a Change in Outcomes

A recent study by Dr. Chapman, published in Circulation, showed that implementation of high sensitivity cardiac troponin (hs-cTn) and the fourth universal definition of myocardial infarction (MI) increased the identification of patients at risk for cardiovascular and non-cardiovascular events, but failed to improve the outcomes. This study warrants the importance of seeking new strategies to improve outcomes in patients with type 2 MI and myocardial injury. Continue reading

Population-Based Cohort Study Shows Blood Pressure Trajectories Over The Life Course Progress More Rapidly in Women Compared to Men

A new study by Dr. Hongwei, published in JAMA Cardiology, demonstrated that blood pressure (BP) trajectories over the life course progress more rapidly in women compared to men, a process that begins as early as the third decade of life. This concept is inconsistent with the previously accepted notion that important vascular disease processes in women occur by 10 to 20 years delay compared to men. These sex-based differences in physiology may establish the cornerstone for future cardiovascular disorders that often present differently in women compared with men.

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Study Shows Hepatitis C Status Not Associated With Adverse Events in Adult Heart Transplant Patients by 1 Year

A recent study by Dr. Kilic, published in the American Heart Association Journal, showed similar adverse outcomes in the 1-year survival, rejection rates, and complications of patients who received a heart transplant using hepatitis C-positive (HCV+) donors whereas those using hepatitis C-negative donors.

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Randomized Trial Shows Prasugrel Associated with Better Endothelial Function and Stronger Platelet Inhibition as Compared to Clopidogrel or Ticagrelor in Patients with ACS Who Undergo Stenting

In a recent randomized, three-arm, parallel, blinded study by Dr. Schnorbus, published in European Heart Journal, prasugrel was associated with improved endothelial function, more potent platelet inhibition, and decreased plasma interleukin (IL)-6 levels in patients undergoing stent placement for acute coronary syndrome (ACS) compared to ticagrelor and clopidogrel. These effects were observed in patients who received prasugrel 2 hours before stenting.

Coronary artery stenting has been associated with impaired coronary and peripheral endothelial function as well as an inflammatory response leading to the release of mediators and subsequent platelet aggregation. These phenomena are associated with in-stent restenosis as well as adverse prognostic outcomes after percutaneous coronary intervention (PCI). Platelet inhibitors, such as P2Y12 receptor inhibitors, are administered prior and after coronary interventions to address these adverse effects. However, previous studies have suggested that differences exist among P2Y12 inhibitors in terms of their efficacy.

In a prospective, single-center study, a total of 90 patients with unstable angina or non-ST elevation myocardial infarction (NSTEMI) undergoing coronary stenting were randomized to receive a single dose of clopidogrel (600mg), prasugrel (60mg), or ticagrelor (180mg) followed by chronic therapy with the same drug. Patients with elevated c reactive protein (CRP), infective or inflammatory disorders, personal history of prior coronary interventions, impaired hepatic/renal function, those with heart failure, and those with ST elevation myocardial infarction (STEMI) were excluded from the study. The primary endpoint of the study was the change in flow-mediated dilation (FMD) of the conduit artery over a period of 1 day, 1 week, and 1 month after PCI. Secondary endpoints were the effect of study medications on macrovascular and microvascular function, platelet aggregation, and inflammatory stress.

The study showed that antiplatelet therapy immediately before stenting was associated with improved FMD without a significant difference among study medications. On the first follow-up after PCI and later follow-up visits, prasugrel was associated with a stronger platelet reactivity inhibition and improved endothelial function. These effects were limited to those who received prasugrel before catheterization. Prasugrel platelet inhibitory effect was more obvious in NSETMI patients than in those with unstable angina. Prasugrel therapy also led to a more pronounced decrease in IL-6 levels. According to the author, “when administered pre-PCI, prasugrel, but not the other agents, limits stent-induced endothelial dysfunction and inflammation in ACS.” This study is limited by its small size and future studies are needed to further confirm these conclusions.


Elevated Coronary Sinus Neuropeptide Y Levels Are Associated With Adverse Outcomes in Patients With Chronic Heart Failure

The study by Dr. Ajijola, published in JAMA Cardiology, found that elevated coronary sinus neuropeptide Y (NPY) level is associated with adverse cardiovascular events in stable patients with chronic heart failure and therefore, it may have prognostic value in this population.

Increased cardiac sympathetic signaling has been associated with adverse cardiovascular outcomes. Biomarkers of the sympathetic system are of significant interest in the assessment of cardiovascular outcomes. NPY is one of the circulating catecholamines, which may predict the risk of death in patients with chronic heart failure.

Dr. Ajijola and his colleagues conducted a prospective observational cohort study at a single-center, tertiary care hospital. They observed 105 patients with stable heart failure undergoing elective cardiac resynchronization therapy (CRT) device implantation between 2013 and 2015. Patients with NYHA class I, severe aortic stenosis, cardiac surgery within prior 90 days, severe obstructive pulmonary disease requiring oxygen or with recent decompensation (< 30 days), current pregnancy, primary pulmonary hypertension, continuous intravenous drug infusion for heart failure, and life expectancy under 6 months were excluded from the study. At the time of the intervention, the coronary sinus blood sample was taken and checked for the NPY levels. Patients were evaluated for major adverse cardiovascular events (MACE) as well as responses to CRT.  Composite endpoint was defined as death, cardiac transplant (OHT), or ventricular assist device (VAD) placement.

The results of the study showed that NPY levels of coronary sinus were associated with prognostic implications in patients with heart failure. 20 out of 105 (19%) patients showed composite endpoints at a median follow-up of 29 months. Also, the NPY levels of greater than 130 pg/mL were associated with worse outcomes compared with those with lower levels (HR, 8.9; 95% CI, 3.1 – 25.7; P < 0.001). The results remained significant even after adjusting for age, eGFR, and LVEF (HR, 9.5; 95% CI, 2.92 – 30.5; P < 0.001).  According to Dr. Ajijola, “Coronary sinus NPY levels may identify patients in whom close clinical monitoring and more aggressive interventions are needed to prevent adverse events. It may also identify those in whom CRT is likely to be ineffective, and such patients may be considered sooner for OHT or VAD.”

This study is limited by some points. First, although NPY levels were irrespective of CRT response, the presence of CRT devices limits the external validity of the study. Second, the sample size was small for formal statistical validation of the study including the NPY thresholds. Future studies are warranted to further validate the results of this study and to clarify the prognostic value of NPY levels.

Persistently Elevated Neuropeptide Y, a Sympathetic Neurotransmitter, is Found to be Associated with Ventricular Arrhythmias in Patients with Myocardial Infarction

The sympathetic drive leading to the release of arrhythmogenic agents after myocardial infarction (MI) is the target of pharmacologic treatment to reduce the mortality associated with post-MI arrhythmias. Beta-blockers, so far, are the only primary prevention antiarrhythmic drugs that decrease the mortality following MI.  However, ventricular arrhythmias still complicate up to 10% of the cases despite sufficient beta-blockade. Additionally, MI has been associated with the release of non-catecholaminergic co-transmitters such as neuropeptide Y (NPY). This cardiac sympathetic co-transmitter can affect calcium electrophysiology of the cardiomyocytes and trigger arrhythmic events.

The new study by Dr. Kalla and his colleagues hypothesized that NPY is the pro-arrhythmic agent after an MI. To evaluate their hypothesis, they monitored 78 patients with ST-elevation MI  treated with primary percutaneous coronary intervention (PPCI) for the development of ventricular arrhythmias. Peripheral venous blood sampling was done at the time of intervention to assess the NPY level. To compare, they also measured the NPY level of peripheral venous blood in 12 candidates of elective angiography of similar age and gender, who had normal coronary arteries.

Ventricular arrhythmias occurred in 7% of the STEMI patients within 48 hours. Their venous NPY level has observed to be significantly (P < 0.05) higher compared to control patients. The author also suggested that an NPY level of 27.3 pg/mL has a sensitivity of 0.83 and a specificity of 0.71 for ventricular arrhythmias threshold. To further evaluate their hypothesis regarding the arrhythmogenic effect of sympathetic-induced NPY release, they experimented with an animal model. Through their rat model experiment, Dr. Kalla demonstrated that despite maximal beta-blockade with metoprolol, prolonged stimulation of the sympathetic system caused an enormous increase in NPY level and subsequent decrease in ventricular arrhythmias threshold. Interestingly, NPY, antagonized by Y1 receptor antagonist BIBO3304, prevented these effects.

The authors added, ” In patients presenting with STEMI treated with PPCI, NPY levels are associated with an increased incidence of ventricular arrhythmia in the immediate postinfarct period, independent of classical risk factors, such as late presentation, larger infarct size, and prior beta-blocker usage.” The author concluded that sympathetic-induced release of NPY is associated with post-MI arrhythmia and drugs reversing its effect work along with beta-blockers as a new anti-arrhythmic therapy.

Interim Results of The EVAPORATE Trial Indicate No Change in Low Attenuation Plaque Volume But A Reduction in Total Plaque Volume Following Treatment with Icosapent Ethyl

The interim results of EVAPORATE trial, a study on the effect of Icosapent Ethyl on coronary plaque progression in statin-treated patients with elevated Triglyceride (TG) level (200-499mg/dl), were presented by Dr. Matthew Budoff at the American Heart Association 2019 meeting. Dr. Budoff and his team found that in patients with coronary atherosclerosis treated with statins, the addition of Icosapent Ethyl​ (Vascepa) was not associated with a change in low attenuation plaque volume but was associated with a decrease in total plaque volume. However, these are preliminary findings and the trial is set for completion at 18 months.

Icosapent Ethyl, a high‐purity eicosapentaenoic acid (EPA) derivative, has been approved as an adjunct to diet for the reduction of TG levels in adults with elevated TG levels. Its utility has been associated with an increase in serum EPA levels, a lower serum TG level as well as a decrease in inflammatory markers. A prior trial investigated the effect of long-term eicosapentaenoic acid (1.8 g/d) on more than 18000 statin-treated patients, in Japan, showed a significant reduction (19%) in the relative risk of major coronary events.

In the EVAPORATE trial, statin-treated patients with coronary atherosclerosis (defined by narrowing≥20% in 1 coronary artery by either invasive angiography or multidetector computed tomography angiography (MDCTA)) and elevated serum TG levels (135-499mg/dl) were enrolled. Exclusion criteria included severe heart failure, hypersensitivity to contrast or fish and renal insufficiency. The primary endpoint of the study was progression rates of low attenuation coronary plaques as measured by MDCTA. The secondary endpoints were the quantitative changes in plaque morphology, inflammatory markers and the relationship between plaque vulnerability and these changes.

A total of 80 individuals participated in the study (40 randomized to receive Icosapent Ethyl and 40 to receive the placebo). Participants were evaluated at baseline, 3 and 9 months of the study. At baseline, each participant underwent a cardiac computed tomography angiography (CCTA) to evaluate plaque morphology and volume as well as its composition. At 9 months, compared to placebo, Icosapent Ethyl slowed low attenuation coronary plaque progression by 21% (p=0.469). Although the primary outcome was statistically insignificant, the study continues until 18 months. Secondary outcomes of the study were promising, including a reduction in total non-calcified plaque volume by 19% (p = 0.01) and a 42% (p <0.0004) reduction in total plaque volume.

In an interview with Dr. C. Michael Gibson, Dr. Budoff discussed the primary findings of the trial. He noted that the increase in serum EPA levels significantly increased in those receiving Icosapent Ethyl and this increase was associated with a coronary plaque regression as well as an anti-inflammatory effect.

This study limited by some points. First, the follow-up duration was shorter than prior studies. Second, the primary endpoint was not statistically significant at the interim time point. The ultimate result of this trial may further define the potential clinical benefits of Icosapent Ethyl on atherosclerotic disorders.

Click here to view the study slides.

Click here to listen to Dr. Budoff and Dr. Gibson discuss the findings of the study.