In an original study conducted by Dr. Aleksandr Voskoboinik et al. recently published in The New England Journal of Medicine, it was found that alcohol consumption is a modifiable risk factor for Atrial Fibrillation (AFib) and abstinence from alcohol in people with AFib causes a reduction in burden and recurrence rates of AFib. Continue reading →

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.

A study led by Dr. Sotirios Tsimikas published in the New England Journal of Medicine showed that the hepatocyte-directed antisense oligonucleotide APO(a)-LRx significantly reduced the blood lipoprotein(a) [Lp(a)] levels in patients with established cardiovascular disease in a dose-dependent manner.

Continue reading →

A study led by Dr. Michinari Hieda published in Circulation showed that left ventricular myocardial stiffness is greater in patients with left ventricular hypertrophy and elevated cardiac biomarkers as compared to healthy controls. This may represent the transitional state from a normal healthy heart to heart failure with preserved ejection fraction (HFpEF).

Continue reading →

Hypertrophic cardiomyopathy (HCM) is the most common inherited genetic disorder of the myocardium, and the number one culprit of sudden cardiac death in athletes, particularly African Americans.

“Is race associated with differential disease expression, inequitable care provision, or disparate clinical outcomes among patients with hypertrophic cardiomyopathy?”

In order to answer the above question, Lauren A. Eberly, et al. studied 2,467 patients with hypertrophic cardiomyopathy. In a retrospective cohort study, black and white patients with hypertrophic cardiomyopathy from the US-based sites of the Sarcomeric Human Cardiomyopathy Registry from 1989 through 2018 compared in terms of baseline characteristics; genetic architecture; adverse outcomes such as cardiac arrest, cardiac transplantation or left ventricular assist device implantation, cardioverter-defibrillator implantation, all-cause mortality, atrial fibrillation, stroke,  prevalence and likelihood of developing heart failure; and receiving septal reduction therapies.

According to the results of this study (8.3 percent black; 91.7 percent white), published in the JAMA CARDIOLOGY (December 2019), compared with white patients, black patients with HCM were younger (mean age, 36.5 versus 41.9 years), were less likely to have sarcomere mutations (26.1 versus 40.5 percent), had a higher prevalence of New York Heart Association (NYHA) class III or IV heart failure at presentation (22.6 versus 15.8 percent) and were more prone to developing heart failure (hazard ratio, 1.45). Lower rates of genetic testing (26.1 versus 40.5 percent) have been observed in black patients. Although there were no racial differences in implantation of implantable cardioverter-defibrillators, the invasive septal reduction was less common among African Americans (14.6 versus 23 percent). Nevertheless, Black patients had fewer incidents of atrial fibrillation (35 [17.1 percent] versus 608 [26.9 percent].

The results of this study were in accordance with the previous studies that mentioned a higher prevalence of complicated hypertrophic cardiomyopathy in African Americans in contrast to the lower prevalence of HCM in this community.  Eberly, et al. believe that racial differences in disease expression and adverse clinical outcomes are not only because of different characteristics of the disease in African Americans but also inequities in clinical care provision might be responsible for these observed differences.

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.

A study led by Dr. Mengyu Fan published in the European Heart Journal showed that a healthy sleep pattern was associated with a lower risk of cardiovascular disease (CVD), congestive heart failure (CHF), and stroke in patients with low, intermediate or high genetic risk.

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 →

Statins, especially high-intensity statins, could reduce the risk of a composite of death, stroke, acute coronary syndrome, or major bleeding as compared to a placebo in patients with acute ischemic stroke and atrial fibrillation. The observational study that was published in the Journal of the American Heart Association highlights the need for a further randomized control trial to further explore this observation.

Continue reading →

In patients with stable coronary artery disease, a decrease in circulating progenitor cell count during exercise is associated with worse disease prognosis compared to the presence of stress-induced myocardial ischemia. The study led by Dr. Kasra Moazzami that was published in JAMA Cardiology highlights the need to identify whether strategies to improve circulating progenitor cell count response during exercise will lead to a better prognosis.

Continue reading →

A study led by Dr. Navakaranbir Bajaj published in Circulation showed that coronary microvascular dysfunction, but not estimated glomerular filtration rate was associated with abnormal cardiac mechanics and an increased risk of cardiovascular events. The findings of this study suggest that coronary microvascular dysfunction may play a role in determining how chronic kidney disease can lead to abnormal cardiac function in patients without ischemic heart disease.

Continue reading →

A study led by Dr. Kathleen Sturgeon published in the European Heart Journal showed that in patients diagnosed with cancer, the majority of cardiovascular deaths in the United States occur in patients diagnosed with breast, prostate or bladder cancer. Additionally, the investigators demonstrated that patients with cancer are at a higher risk of dying from cardiovascular disease as compared to the general population.

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.

The results of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches – Chronic Kidney Disease were presented by Dr. Sripal Bangalore at the American Heart Association 2019 meeting. Dr. Bangalore and his team showed that in patients with moderate ischemia and end-stage renal disease, an initial invasive strategy with catheterization and possibly percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) did not lead to an improvement in clinical outcomes.

Continue reading →

An expanded analysis of 231 patients from the GALILEO trial comparing rivaroxaban-aspirin based anti-thrombotic therapy with clopidogrel-aspirin based dual anti-platelet therapy post transcatheter aortic valve replacement (TAVR), has shown that the rivaroxaban based regimen protects from valve leaflet motion abnormalities. The rivaroxaban based strategy led to decreased prosthetic valve leaflet thickening and motion reduction following TAVR performed for severe aortic valve stenosis. Continue reading →

Dr. John McMurray presented the results of the DAPA-HF trial at the American Heart Association 2019 Meeting. The study, which was published in the New England Journal of Medicine, showed that dapagliflozin, an SGLT-2 inhibitor, can potentially be used to treat heart failure with reduced ejection fraction (HFrEF) in patients with and without type 2 diabetes.

Continue reading →

During the American Heart Association 2019 meeting, Dr. Kosh Ray presented the results of the BETonMACE trial. Dr. Ray and his teams showed apabetalone, a BET protein inhibitor was safe and well-tolerated and could potentially be used to reduce the risk of major adverse cardiovascular events (MACE).

Continue reading →

The results of a phase 1 trial that evaluated the safety of RUC-4, a novel subcutaneous GPIIb/IIIa inhibitor, were presented by Dr. Dean Kereiakes at the American Heart Association 2019 meeting. The study showed that in healthy volunteers and subjects on aspirin with stable coronary artery disease (CAD), RUC-4 provided rapid and high-grade platelet inhibition that resolved within 2 hours.

Continue reading →

The results of the GALILEO trial were presented by Dr. George Dangas at the American Heart Association 2019 meeting. The trial, which was stopped early, showed that in patients with a successful transcatheter aortic valve replacement (TAVR), a rivaroxaban-based strategy was associated with excessive ischemic and bleeding events.

Continue reading →