A recent study by Dr. Duthoit, MD, published in Circulation: Cardiovascular Interventions, showed that compared to dual antiplatelet therapy, nonvitamin k antagonist monotherapy using a reduced dose of rivaroxaban (10 and 15 mg) in patients undergone left atrial appendage closure was associated with lower thrombin generation. This data supported that reduced rivaroxaban doses could be a substitute for the antithrombotic medications currently used after this procedure. Continue reading →

A recent meta-analysis of clinical trials with more than 100,000 patients has shown that the carotid intima-media thickness (cIMT) progression can be used as a surrogate marker for cardiovascular risk in the clinical trials. The results of this study published in Circulation. According to Dr. Willeit, the assessment of cIMT progression can provide a link for the development and license of new therapies for cardiovascular disease. Continue reading →

A recent study by Dr. O’Donoghue, published in Circulation, shows that early aspirin discontinuation with continued P2Y12 inhibitor monotherapy, after the percutaneous coronary intervention (PCI),  was associated with a significant reduction in major bleeding compared to dual antiplatelet therapy. This study did not show a significant increase in major adverse cardiovascular events (MACE) after aspirin discontinuation in the participants.
Continue reading →

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.
Continue reading →

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.
Continue reading →

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 →

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 →

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.

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.

Continue reading →

Maria Trinidad Soria-Florido et al. published the results of their study on high-density lipoprotein (HDL) function and coronary syndrome in Circulation. They showed that low amount of HDL sphingosine-1-phosphate (S1P) and apolipoprotein A-I and low cholesterol efflux capacity are associated with cardiovascular manifestations of angina. HDL function was studied by measuring cholesterol efflux capacity, S1P, and ApoA-I in apolipoprotein B-depleted plasma and they showed that impaired cholesterol function is associated with a higher risk of acute coronary syndrome (ACS), irrespective of HDL cholesterol (HDL-C) concentrations.

The investigators selected a subgroup of patients who were participating in PREDIMED study, which was a randomized clinical trial including patients with high cardiovascular risk factors to evaluate the effects of following a traditional Mediterranean Diet (TMD) on the primary prevention of cardiovascular outcomes. The primary endpoints were decided to be fatal or non-fatal myocardial infarction and/or fatal or non-fatal unstable angina. The committee responsible to adjudicate the events was blinded to the treatment. Dr. Trinidad et. al. implemented a nested 1:2 case-control design, matching two controls by age (±5 years), sex, body mass index, intervention group, and time-to-event. They obtained apolipoprotein B-depleted plasma samples and measured the HDL related activity in the sample.

The findings showed that except for plasma HDL-C concentrations and the levels of ApoA-I in HDL, all other HDL related biomarkers correlated weakly with each other. There was an almost linear correlation between all HDL related biomarkers (except for ApoA-IV) and the incidence of cardiovascular events. They also showed that there is a strong relationship between low cholesterol efflux capacity (CEC) and a higher incidence of myocardial infarction.

Previous studies have shown that there is an association between low CEC and ACS in hypertriglyceridemia patients, but Maria Trinidad Soria-Florido et al. showed that this association also exists in patients with normal triglyceride levels. Hypertriglyceridemia probably exaggerates the effect. They also showed that not only HDL-bound S1P can predict atherosclerotic lesions development and its extent, but also S1P levels in apolipoprotein B-depleted plasma is associated inversely with ACS risk.

The study was limited by the small sample size and lack of thorough evaluation of the HDL oxidative-inflammatory index.

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.

Continue reading →

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.

Raphael et al. showed in a prospective cohort study, published in Circulation, that type 2 myocardial infarction (T2MI), defined as an acute imbalance between oxygen delivery to the myocardium and the demand of the myocardium in the absence of athero-thrombosis, is associated with higher all-cause mortality compared to type 1 myocardial infarction (T1MI) caused by athero-thrombotic events, with no difference between these 2 groups regarding cardiovascular death.

Raphael et al. retrospectively included 5,460 patients with high troponin levels (more than 0.01) and divided them into 2 groups of T1MI and T2MI. They followed up the patients for 5.5 years. Cases with prior MI were excluded from the analysis.

After including the cases, they retrospectively classified MI types by 2 cardiologists based on clinical signs and laboratory results. MI was defined by a rise and/or fall in cardiac troponin T (cTnT) associated with either ischemic symptoms, new/presumed new ECG changes, new imaging evidence of ischemia, or direct identification of intracoronary thrombus on angiogram or autopsy. The cardiologists defined T2MI based on elevated cardiac troponin without other necessary factors. Other different types of MI including procedure-related MI were categorized as T1MI. They encountered the first MI event as the main event in cases with multiple MI events. They further subclassified T2MI based on its cause to the following subclasses: Arrhythmia, hypotension, anemia, post-surgical status  (in the absence of other causes e.g., T1MI and arrhythmia), hypoxia, and other (including spontaneous coronary artery dissection, coronary embolism, coronary spasm, structural heart disease e.g., severe aortic stenosis and malignant hypertension). They prospectively gathered the information regarding the mortality cause in the patients from the available documents, and divided the cause of mortality into either cardiovascular or non-cardiovascular.

The results showed that 56% were adjudicated as T1MI and 43% as T2MI. Patients with T2MI were older, female gender predominant, with a higher prevalence of chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) while patients with T1MI were more likely to present with other well known MI risk factors. They also showed a lower level of sufficient MI related medical treatment in the T2MI group compared to T1MI. The rate of MI in both types has shown a decrease in incidence in the population. The rate of all-cause mortality was calculated after sex and age adjustment, and results implicated that the all-cause mortality rate was significantly higher in T2MI compared to T1MI even after adjustments. They showed that the risk of cardiovascular death is the same in both T1MI and T2MI, which may indicate the necessity of better diagnosis and treatment of T2MI after an encounter.

There is a lack of information regarding the T2MI incidence and effect on mortality in the general population. Raphael et al. tried to add to our current knowledge regarding this common type of MI by addressing the effect of this condition on all-cause and cardiovascular mortality.

One of the major factors encountered as a limitation for this study may be the difficulty faced in the diagnosis of T2MI in the clinical setting. A question has still remained that if treatment of T2MI with the same treatment protocol as T1MI will help to decrease cardiovascular and all-cause mortality in the patient’s population.

The positive effect of the remote patient management (RPM) intervention on morbidity and mortality, seen in the Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial was no longer observed 1 year after stopping the RPM intervention. The extended follow-up results of the TIM-HF2 trial led by Dr. Koehler (Department of Cardiology and Angiology, Centre for Cardiovascular Telemedicine, Charité–Universitätsmedizin Berlin, Berlin, Germany) was recently published in the Lancet. Continue reading →

In a large population-based study, a significant and sustained survival benefit was observed in patients with out-of-hospital cardiac arrest treated at teaching hospitals. The report of the study led by Dr. Czarnecki was recently published in Circulation: Cardiovascular Quality and Outcomes. Continue reading →

One in eight patients with atherosclerotic cardiovascular disease reports medication nonadherence due to cost, according to a nationally representative survey of more than 14,000 US adults. The findings of the study led by Dr. Rohan Khera (University of Texas Southwestern Medical Center, Dallas, US) was recently published in Circulation.

Continue reading →

The results of the COMPLETE Optical Coherence Tomography Substudy were presented by Dr. Natalia Pinilla-Echeverri at the American Heart Association 2019 meeting. The substudy found that in patients with an ST-elevation myocardial infarction and multivessel coronary artery disease, half of the patients had a non-culprit lesion with vulnerable plaque morphology.

The COMPLETE trial previously demonstrated that routine angiography guided staged a percutaneous coronary intervention (PCI) of non-culprit lesions reduced the composite endpoint of cardiovascular death or myocardial infarction by 26%. However, whether the benefit of routine PCI of non-culprit lesions is, as a result, the non-culprit lesions having characteristics that were consistent with a vulnerable plaque is not known. Optical coherence tomography (OCT) is a form of intracoronary imaging that is able to identify vulnerable plaques. OCT is able to recognize thin cap fibroadenoma (TCFA), an indicator of a vulnerable plaque that is at risk of rupturing. The investigators wanted to identify the prevalence of TCFA in obstructive compared to non-obstructive non-culprit lesions.

In the COMPLETE trial, patients with a STEMI and multivessel disease who underwent successful PCI of the culprit lesion were randomized to either routine staged PCI of all suitable non-culprit lesions with the goal of complete revascularization regardless of whether there were clinical symptoms or evidence of ischemia or culprit-lesion revascularization only. Patients were deemed to have multivessel disease if they had angiographically significant non-culprit vessel disease of a vessel that was at least 2.5mm in diameter. A lesion was considered angiographically significant if it had at least 70% stenosis of the vessel diameter or 50-69% stenosis with a fractional flow reserve of less than 0.8. In this substudy, STEMI patients with stenosis of at least one non-culprit vessel with more than 70% stenosis that was suitable for OCT were identified. After randomization, multivessel OCT imaging was performed on vessels with non-culprit lesions that underwent PCI, additional vessels with or without target non-culprit lesions for PCI, and STEMI vessels with segments more than 50mm that were unstented.

A total of 93 patients and 425 lesions were included in this substudy. The baseline characteristics in the main study were similar to this imaging study. The average age was 61.3, 82.8% were male, 12.9% had diabetes, 64% had 1 residual diseased vessel and 36% had two or more residual diseased vessels. The non-culprit lesions were classified according to whether they had significant stenosis and whether they had a TCFA. Of the lesions with greater than 70% obstruction, 58 (38.7%) had a TCFA and 92 did not. Of the lesions with less than 70% obstruction, 74 (23.2%) had a TCFA and 201 did not. When assessing the prevalence of TCFAs per patient, the investigators found that half of the patients with TCFA had an obstructive non-culprit lesion that contained vulnerable plaque.

In an interview with Dr. Arzu Kalayci, Dr. Pinilla-Echeverri discussed the implications of the study. She said, “this is very important in the STEMI population because we believe the STEMI population has higher rates of future cardiovascular events. IT may all be related to the inflammatory response that is behind [this]. This is telling us that these patients had a definitely higher risk because they had vulnerable plaques far from the culprit segment. This is reassuring that acute coronary syndrome implies a diffuse pathophysiology with vulnerable plaque not only in the culprit segment but in places far away from the culprit lesion. These results support the findings in the COMPLETE trial.” However, this study does have its limitations. The substudy was observational and is affected by confounding and bias. The substudy was not powered to link clinical evens to morphology. Regardless, the findings of this study could potentially explain the benefit of routine PCI of obstructive non-culprit lesions in patients with STEMI and multivessel disease.

Click here to view the study slides.

Click here to listen to Dr. Kalayci and Dr. Pinilla-Echeverri.

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.

11/6/2019- Joe X. Xie et. al recently published the results of a Veterans cohort study in Circulation. They were able to show a meaningful decline in the rate of important 4 post-PCI medication utilization (beta-blockers, statins, ACEI/ARB, and P2Y12 inhibitor) among Veterans in a follow-up period of 5 years, with the highest decrease in medication utility after the first year of PCI. They also showed continuous consumption of all these medications is associated with a decreased rate of major adverse cardiac events (MACE).

Medical therapy utilization and association between medical therapy and MACE were the study’s primary outcomes. They included 57,900 patients who underwent staged PCI, defined as PCI on a non-STEMI lesion and if the PCI is being performed on a segment that had not been treated before. They excluded patients who were in the setting of cardiogenic shock, those who did not survive the index hospitalization following PCI, patients who obtain all their medications outside the VA, or those with a documented allergy to any of the four medication classes of interest. The majority were white elderly males, they usually used tobacco (62%), and most of them had comorbidities including hypertension (89.4%), diabetes mellitus (47.1%), and hyperlipidemia (88.4%) as main comorbidity factors. The mean duration of follow-up was 5 years. During an average follow-up of 5 years, a total of 24,364 patients experienced MACE which was defined as the first occurrence of all-cause death, rehospitalization for MI, rehospitalization for stroke, or repeat revascularization throughout the follow-up. They found a statistically significant correlation between death reduction and stroke rehospitalization and medication utility up to 5 years after PCI but not rehospitalization for MI. In their analysis, Xie and his colleagues calculated that less than 60% of the patients undergoing PCI receive all 4 medication classes at discharge (β-blocker, statin, ACE inhibitor/ARB, and P2Y12 inhibitor), with a gradual decrease of medication utility for approximately 20% of statins, β-blockers, and ACE inhibitor/ARBs over the subsequent 5 years post-PCI. This rate was reported to decrease to approximately 70% for the use of P2Y12 inhibitors.

Previously, there was little evidence available concerning the rate of long-term use of medical therapy following PCI. It has been shown that there is a suboptimal medication adherence by patients 6-12 months after PCI. Xie et al. also showed that all the described medication therapy classes were associated with decrease in the MACE risk even at 5 years post-PCI. They also noticed that all 4 classes of medications were associated with decreased MACE rates.

The data shown by Xie et al. can help with understanding patient compliance to medications, and to implement methods to increase the compliance. Further studies for non-VA patients are recommended.

The result of a study, presented at ACC 2019 in March, 2019 and recently published in JACC Interventional Cardiology, showed that despite angiographically successful percutaneous coronary intervention (PCI), physiological assessment detected residual ischemia in 1 out of 4 patients after coronary stenting. The majority of the cases were due to inappropriate focal lesions which seem amenable to treatment with additional PCI.

Continue reading →