C. Michael Gibson, MD, CEO non-profit Baim / PERFUSE Research Institute, Harvard Professor, Cardiologist BIDMC, Founder & Chairman WikiDoc.org speaks about ACC 2021 Abstract - Early And Late Recurrent Cardiovascular Risk In Patients With Recent Acute Coronary Syndrome - Meta-Analysis And Implications In Trial Design
Link to Article: abstractsonline.com/pp8/#!/9228/presentation/22780
Despite receiving excellent medical treatment, people with an acute coronary syndrome have a significant residual atherosclerotic risk (ACS). The goal of this research was to calculate the risk of early and late major adverse cardiovascular events (MACE) and consider the implications for trial design. Methodologies: To find phase III interventional studies on high-risk ACS patients, a thorough search was conducted. Meta-analytic techniques were used to estimate pooled incident rates at 90 and 360 days by fitting a random-effects model using the DerSimonian-Laird technique. The connection between power and relative risk reduction (RRR) or absolute risk reduction (ARR) for early vs. late MACE endpoints was investigated using the log-rank test (n=10,000; 1-sided=0.025).
The following are the outcomes:
A total of 82,727 high-risk individuals with recent ACS were examined from seven studies. After 90 days, the pooled rate of recurrent MACE was 4.1 percent (95 percent CI: 3.0 percent-5.7 percent), and at 360 days, the rate was 8.3 percent (95 percent CI: 7.1 percent -9.8 percent). Within the first 90 days, approximately 49% of incidents happened. For late MACE, a lower RRR (22 percent vs. 30 percent) is required to achieve 90 percent statistical power, but for early MACE, a lower ARR is required (1.2 percent vs. 1.8 percent ).
The first 90 days after an ACS occurrence are most sensitive to recurrent MACE. Determining a clinically meaningful benefit by relative vs. absolute risk reduction may impact the choice of early vs. late MACE as the research endpoint from a trial design standpoint.
C. Michael Gibson, MD, CEO non-profit Baim / PERFUSE Research Institute, Harvard Professor, Cardiologist BIDMC, Founder & Chairman WikiDoc.org speaks about ACC 2021 Abstract - 1063-07 - Association Of Cholesterol Efflux Capacity With Adverse Cardiovascular Outcomes - A Meta Analysis
The principal process by which macrophages remove cholesterol from atherosclerotic plaque is reverse cholesterol transport. A systematic literature review and meta-analysis were done to investigate the relationship between cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and poor cardiovascular (CV) events.
A literature study was conducted to gather papers that looked at the link between CEC and CV outcomes. Adverse CV events, a composite of incident atherosclerotic CV disease (acute coronary syndrome, stroke/transient ischemic attack, revascularization, or new atherosclerotic plaque), or all-cause death, were the main outcomes.
The following are the outcomes:
Twenty investigations yielded a total of 25,132 individuals. High CEC levels were linked with a 37 percent decreased risk of the main outcome when compared to low CEC levels (RR=0.63; 95 percent CI, 0.52-0.76; P0.00001; Figure A). A 20 percent decreased risk of unfavorable CV events was related with every SD rise in CEC (HR=0.80; 95 percent CI, 0.66-0.97; P=0.02). After controlling for CV risk factors, medicines, and HDL concentration, the link remained significant (HR=0.76; 95 percent CI, 0.63-0.91; P=0.004). There was a 5% risk decrease in unfavorable CV events for every 0.1 unit rise in CEC (RR=0.95; 95 percent CI, 0.91-0.99; Figure B).
Higher CEC is linked to less negative CV outcomes. These findings call for more research on CEC as a possible therapeutic target in order to enhance clinical outcomes.
Thomas M. Roston, MD, FRCPC from The University of British Columbia speaks about Burst Exercise Testing Can Unmask Arrhythmias in Patients With Incompletely Penetrant Catecholaminergic Polymorphic Ventricular Tachycardia.
Cardiac arrest following abrupt exercise is a symptom of catecholaminergic polymorphic ventricular tachycardia (CPVT). Standard exercise stress testing (EST), on the other hand, is insensitive, resulting in misdiagnosis and undertreatment. We report on six patients who had a unique burst exercise test, which was characterized by a sudden high workload at the start of testing, after a nondiagnostic conventional progressive EST. Compared to conventional EST, burst EST caused new and more complicated arrhythmias in 5 of 6 patients, necessitating medication treatment in 3 individuals. This minor EST adjustment might increase diagnostic sensitivity and treatment decision-making by better mimicking a common CPVT triggering event.
Paul W. Armstrong, MD from the Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada and the Merck speaks about the ACC 2021 Abstract - Coronary Artery Disease and Cardiovascular Outcomes in Heart Failure: Insights from the VerICiguaT Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA).
The trial's purpose was to compare vericiguat to placebo in individuals with chronic heart failure (CHF) caused by a low ejection fraction (EF). Vericiguat boosts the activity of soluble guanylate cyclase. This may assist to enhance cardiac and vascular function by increasing the generation of cyclic guanosine monophosphate.
Design of the Research
* This is a randomized sample.
* Double-blind study
Vericiguat (n = 2,526) versus placebo (n = 2,524) were given to CHF patients. Vericiguat was begun at 2.5 mg per day, then raised to 5 mg, then 10 mg per day.
* The total number of students enrolled is 5,050.
* Follow-up period: 12 months
* The average patient is 68 years old.
* Females account for 24% of the total.
Criteria for inclusion:
* CHF; New York Heart Association class II-IV, left ventricular EF 45%, and heart failure treatment based on guidelines.
* A recent hospitalization for heart failure or the administration of an intravenous diuretic
* Natriuretic peptides elevated; N-terminal pro–B-type natriuretic peptide (NT-proBNP) 1000 pg/ml (1600 pg/ml if atrial fibrillation) or BNP 300 pg/ml (500 pg/ml if atrial fibrillation).
* Clinically stable (systolic blood pressure 100 mm Hg for 24 hours and no IV diuretics)
Criteria for exclusion:
* Nitrates with a lengthy half-life, phosphodiesterase type 5 inhibitors, and riociguat
* Awaiting a heart transplant, using continuous intravenous diuretics, or using a ventricular assist device now or in the future.
* Dialysis or chronic renal disease (evaluated glomerular filtration rate of 15 ml/min/1.73 m2)
* Severe pulmonary illness that necessitates the use of oxygen on a continual basis
* Hepatic insufficiency (severe)
* Cardiovascular comorbidities that can be treated
Other noteworthy features/characteristics include:
* The average EF is 29%.
* In 89 percent of cases, the target dosage of vericiguat was met.
The Most Important Findings:
Cardiovascular mortality or heart failure hospitalization occurred in 35.5 percent of the vericiguat group compared to 38.5 percent of the placebo group (hazard ratio [HR] 0.90, p = 0.019). The major outcome risk for vericiguat vs. placebo was 0.84% for those aged 75 years and 1.04% for those aged 75 years (p for interaction = 0.030).
Secondary effects include:
* Cardiovascular death: 16.4% in the vericiguat group vs. 17.5 percent in the placebo group (p = 0.27)
* Death from any cause: 20.3 percent in the vericiguat group vs. 21.2 percent in the placebo group (p = 0.38)
* Hospitalization for heart failure: 27.4 percent of the vericiguat group vs. 29.6 percent of the placebo group (p = 0.048).
* Serious adverse event: 32.8 percent of the vericiguat group versus 34.8 percent of the placebo group had a serious adverse event.
A new technique of boosting soluble guanylate cyclase activity with vericiguat proved successful in individuals with CHF who had recently decompensated. Vericiguat was shown to be more efficacious than placebo in lowering cardiovascular mortality and hospitalization for heart failure. There was a possibility of a greater advantage for those above the age of 75. Vericiguat did not appear to reduce all-cause mortality when compared to placebo. Vericiguat was well tolerated and did not need renal function or electrolyte monitoring. Vericiguat might be a potential therapy option for individuals who have recently had heart failure decompensation.
Jim Januzzi, MD, Director, Dennis and Marilyn Barry Fellowship in Cardiology Research, Massachusetts General Hospital Cardiology Division speaks about American College of Cardiology studies will explore whether AI can improve clinicians' guideline adherence.
The American College of Cardiology (ACC) is preparing three trials to see if customized clinical guideline assistance given at the point of treatment by an AI tool may enhance cardiac patient outcomes.
HealthReveal's software will be used in each of the TRANSFORM trials to develop and give care recommendations based on current best practices. The electronic health record (EHR) system provides doctors with these insights, which include medical literature that informs the software's suggestions.
The research is part of ACC's TRANSFORM project, which began in 2019 and is a new type of quality research program. The pharmaceutical and medical device industries, health plans, employers, doctors, and patients are all involved in these initiatives, which use EHR data, office-based treatments, and collaborations.
In order to fuel the study, ACC teamed with Veradigm, a health information technology firm owned by Allscripts, to build clinical quality improvement and research networks as part of the TRANSFORM initiative. The Pinnacle Registry, which focuses on coronary artery disease, hypertension, heart failure, atrial fibrillation, and diabetes in outpatient settings, and the Diabetes Collaborative Registry are both owned and operated by Veradigm.
These outpatient registries are used by all of the TRANSFORM programs to assist identify providers and patients who are qualified to participate in the program.
The TRANSFORM HFrEF research will be the ACC's first study as part of its collaboration with HealthReveal. It will be directed by Jim Januzzi, M.D., a cardiology researcher at Massachusetts General Hospital, and will focus on the management of patients with heart failure and a low ejection fraction (HFrEF).
Effective treatment techniques have already been discovered, according to Januzzi, who is also a trustee of the ACC and a professor of medicine at Harvard Medical School.
According to 2018 research, fewer than a quarter of HFrEF patients got medication therapies as indicated by current clinical recommendations, and less than 1% of those prescriptions were filled at the correct dosage. Patient outcomes may be deteriorated as a result of noncompliance, as well as greater expenditures for extra care.
The clinical AI software's merits, according to Januzzi and Lonny Reisman, M.D., founder, and CEO of HealthReveal, are its scalability and capacity to update suggestions during the course of therapy. According to Reisman, the tool is also transparent about how it comes to its findings, which is crucial for winning doctors' trust and ensuring that care follows the guidelines.
Hertzel C. Gerstein, MD, MSc, FRCPC, professor and population health institute chair in diabetes research at McMaster University and Hamilton Health Sciences speaks about AMPLITUDE-O: Efpeglenatide reduces CV events, CKD progression in high-risk type 2 diabetes. American Diabetes Association Scientific Sessions.
Data demonstrate that a new GLP-1 receptor agonist decreased cardiovascular event risk by 27% and renal disease progression by 32% in high-risk people with type 2 diabetes, with or without prior SGLT2 inhibitor treatment, when compared to placebo.
The AMPLITUDE-O trial found that weekly efpeglenatide, an investigational exendin-4-based GLP-1 receptor agonist, was safe for high-risk patients and had CV and renal benefits comparable to other human-based GLP-1 receptor agonists in the class, according to data presented at the American Diabetes Association Scientific Sessions and simultaneously published in The New England Journal of Medicine, according to Hertzel. According to him, the study was also the first major CV outcomes trial to evaluate the use of a GLP-1 receptor agonist in a population on background SGLT2 inhibitor treatment, which accounted for 15% of the trial participants.
GLP-1 effects in nonhumans
Four GLP-1 receptor agonists with human GLP-1-like structures have been demonstrated to lower the incidence of cardiovascular events in individuals with type 2 diabetes. The impact of efpeglenatide, an exendin-4-based GLP-1 receptor agonist, on cardiovascular and renal outcomes in high-risk people with type 2 diabetes remains unknown.
Gerstein and colleagues looked at data from 4,076 people with type 2 diabetes, a history of CVD or renal disease, and at least one CV risk factor (mean age, 65 years; 33 percent women; 87 percent white), who were recruited from 344 locations in 28 countries. The average duration of diabetes was 15.4 years, and 90 percent of the participants had previous CVD, with 32 percent having a glomerular filtration rate of less than 60 mL/min/1.73 m2. Researchers randomly allocated patients to receive weekly subcutaneous efpeglenatide 4 mg or 6 mg (n = 2,717) or placebo (n = 1,359), with SGLT2 inhibitor usage (n = 618) stratifying randomization.
The main outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV or unexplained causes as the first major adverse CV event.
During a median follow-up of 1.81 years, major adverse CV events occurred in 189 participants (7%) who were given efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) who were given placebo (5.3 events per 100 person-years), for an HR of 0.73 (95 percent CI, 0.58-0.92; P =.0069 for superiority). The HR for efpeglenatide vs. placebo for the secondary expanded outcome of significant adverse CV events, coronary revascularization, or unstable angina was 0.79. (95 percent CI, 0.65-0.96).
Morten Krogh Christiansen, MD, Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark speaks about Polygenic Risk Score–Enhanced Risk Stratification of Coronary Artery Disease in Patients With Stable Chest Pain.
Although polygenic risk scores (PRSs) have been linked to coronary artery disease (CAD), the therapeutic utility of utilizing PRSs for risk stratification at the single-patient level has yet to be determined. We wanted to see if adding a PRS to clinical risk factors (CRFs) improved risk classification in individuals who were referred for coronary computed tomography angiography because they were suspected of having obstructive CAD.
We recruited 1617 patients with stable chest symptoms and no history of CAD who were referred for coronary computed tomography angiography in this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease). Age, sex, symptoms, past or active smoking, antihypertensive medication, lipid-lowering treatment, and diabetes were all utilized as CRFs for risk classification. Patients' genotypes were also determined, as well as their PRSs. A coronary computed CT angiography was performed on all of the patients. Invasive coronary angiography with fractional flow reserve was also performed on patients suspected of having a 50% stenosis. Visual invasive coronary angiography stenosis >90%, fractional flow reserve 0.80, or quantitative coronary analysis stenosis >50% if fractional flow reserve measurements were not possible were used to establish a combined endpoint of obstructive CAD.
Independent of CRFs, the PRS was linked to obstructive CAD (adjusted odds ratio, 1.8 [95 percent CI, 1.5–2.2] per SD). The PRS showed a 0.63 (0.59–0.68) area under the curve, which was similar to that of age and sex. When the PRS and CRFs were combined, the CRF+PRS model had an AUC of 0.75 (0.71–0.79), which was 0.04 higher than the CRF model (P=0.0029). The use of pretest probability (pretest probability) cutoffs of 5% and 15% resulted in a net reclassification improvement of 15.8% (P=3.1104), with a down-classification of risk in 24 percent of patients (211 of 862) who had a pretest probability of 5% to 15% based on CRFs alone.
Beyond CRFs, adding a PRS enhanced risk classification of obstructive CAD, indicating that PRSs might be used to guide diagnostic testing in the modern clinical context.
Robert H. Eckel, MD, Division of Endocrinology, Metabolism, and Diabetes, Division of Cardiology, University of Colorado Anschutz Medical Campus speaks about Review Article - Cardiovascular effects of omega-3 fatty acids: Hope or hype?
After a clinical trial (REDUCE-IT) revealed excellent outcomes with icosapent ethyl (IPE) in patients undergoing maximally tolerated statin treatment, omega-3 fatty acids have emerged as a novel alternative for reducing the residual risk of cardiovascular disease (CVD) in the statin era. Another experiment (STRENGTH) that employed a high dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) combination failed. These findings pose clinically significant issues when taken together. Are the effects of omega-3 fatty acids neutral, helpful, or perhaps detrimental in individuals on statin therapy? Different kinds of omega-3 fatty acids (just EPA or EPA + DHA), dosages (greater vs. lower dose) of omega-3 fatty acids, or comparators (corn oil or mineral oil), as well as the underlying severity of the CVD risk or usage of statins, might explain the present conflicting results. In addition to these topics, we will examine the biological and clinical consequences of various kinds of omega-3 fatty acids, as well as how to assess the findings of historical and current clinical research and provide practical recommendations for patient treatment.
Fungal infective endocarditis is an uncommon and dangerous kind of endocarditis that can cause significant morbidity and death. Patients with implanted prosthetic valves, implantable cardiac devices, and intravenous drug usage have the highest risk of infection. We describe the case of a 45-year-old man who was diagnosed with Candida parapsilosis endocarditis after having a previous bioprosthetic mitral valve. Splenic infarcts were seen on computed tomography imaging of the abdomen, and transesophageal echocardiography revealed a 1.23 cm x 0.55 cm lesion on the bioprosthetic valve and a 1.02 cm x 0.545 cm lesion on the bioprosthetic valve. The patient was then given Amphotericin B and Fluconazole for the rest of his life. The imaging results and therapy of an uncommon disease process are highlighted in this instance.
Fungal infective endocarditis (IE) is an uncommon and dangerous type of infective endocarditis (IE), with death rates as high as 50% . Prosthetic valve implantation, cardiac implantation devices, and intravenous drug usage are all common risk factors . Candida and Aspergillus species are the most frequent causative agents of fungal IE in general . Candida parapsilosis (n = 8, 67 percent ), Candida glabrata (n = 3, 25 percent ), and Candida albicans (n = 1, 8 percent ) were determined to be the most frequent species in a six-year case analysis of 12 distinct instances of Candida IE . Treatment of Candida IE with Amphotericin B with or without Flucytosine or high-dose echinocandin therapy, followed by life-long maintenance therapy with an oral azole, is recommended by the Infectious Diseases Society of America Candidiasis and the American Heart Association Endocarditis guidelines . Treatment failure with medical care alone is frequent, however, since Candida species have evolved survival tactics that include the development of biofilms on native and artificial heart valves, which can result in low antifungal efficacy . As a result, it's critical to include a surgical option in the treatment of native valve endocarditis, especially in patients with prosthetic valves, because early intervention has been shown to be advantageous . Despite medicinal and surgical therapy, the general prognosis for fungal IE is poor, and active risk factor control is essential.
We present a case of a 45-year-old man with Candida parapsilosis IE in the setting of a bioprosthetic mitral valve, highlighting the computed tomography (CT) abdomen and pelvis, transthoracic echocardiography (TTE), and transesophageal echocardiography (TEE) image findings associated with this deadly disease.
Presentation of a Case:
A 45-year-old man arrived with four months of increasing abdominal distention. He had a history of intravenous drug use, liver cirrhosis related to hepatitis C, recent mitral valve endocarditis with a bioprosthetic mitral valve in 2019, gastroesophageal reflux disease (GERD), and pancytopenia. During the coronavirus-19 epidemic, the patient lost his insurance and stopped receiving normal healthcare. His abdomen distention resulted in a 40-pound unintended weight reduction due to decreased hunger and early satiety. The patient claimed that his GERD symptoms were well-controlled with daily pantoprazole and denied any concomitant symptoms of nausea, vomiting, or diarrhea. Prior to admission, the patient had been experiencing intermittent fevers for two weeks and shortness of breath for three days.
The patient was feverish with a temperature of 101°F, normotensive with a blood pressure of 116/77 mmHg, tachycardia with a heart rate of 114 beats per minute, and saturating 98 percent on room air at the time of admission.
Fungal prosthetic valve IE is an uncommon kind of IE that affects people all over the world. A previous literature analysis found 152 occurrences between 1995 and 2000, with intravenous injection drug usage being recognized as a risk factor in just 4.1% of cases . Fungal IE is linked to high rates of severe morbidity and death, with total morbidity ranging from 67% to 37% and a six-month mortality risk of 37% [4,5]. There has been a scarcity of published studies and medical guidelines regarding the proper selection and duration of antifungal medication. Medical management with liposomal Amphotericin B (LAmB) 5 mg/kg/day (300 mg/day) and Flucytosine 150 mg/kg/day (9 g/day) as part of an initial treatment after positive blood cultures for Candida is the indicated intervention in those case reports that have been published . The most recent Infectious Diseases Society of America (IDSA) guidelines from 2016 include recommendations for treating Candida infections in contaminated pacemakers, implanted cardiac defibrillators, ventricular assist devices, and native and prosthetic valve IE . High-dose echinocandin therapy (Caspofungin 150 mg daily, Micafungin 150 mg daily, or Anidulafungin 200 mg daily) or high-dose echinocandin therapy (Caspofungin 150 mg daily, Micafungin 150 mg daily, or Anidulafungin 200 mg daily) are recommended in these guidelines . In addition, for patients who are unable to undergo valve replacement, chronic long-term suppression with Fluconazole 400-800 mg daily is strongly recommended . Our patient continues to see cardiology as an outpatient. In March 2021, echocardiography revealed decreased visibility of the bioprosthetic valve vegetation and a steady mitral valve peak velocity of 2.06 m/s.
Recent clinical investigations have added to our understanding of Candida IE. Rivosky et al. followed 46 patients with prosthetic valve IE for a median of nine months who were treated with LAmB vs echinocandin-based induction treatment. When compared to patients who got just echinocandins, patients who received only LAmB had a higher six-month survival rate (adjusted odds ratio: 13.52, 95 percent confidence interval 1.03-838.10) . In addition, 21 patients were given long-term Fluconazole maintenance treatment for an average of 13 months, with minimal side effects . Furthermore, as compared to the group treated with medical treatment, the 19 patients who received a cardiac surgical operation did not have improved survival outcomes over a six-month period . The Infectious Diseases Society of America and the European Society of Clinical Microbiology and Infectious Diseases recommendations, which advocate early surgical intervention for all patients with prosthetic IE [5,8], are in conflict with these findings. Despite the limited sample size and low statistical power, this study offers insight into medicinal care as an alternative to surgical surgery.
Candida IE is an uncommon pathogenic condition that has a high proclivity for infecting and compromising implanted prosthetic valves and cardiac devices. People who have used drugs in the past are at the highest risk among the general population. The patient in our instance had previously had bioprosthetic mitral valve replacement and was discovered to have recurrent IE on his bioprosthetic mitral valve. The patient was ultimately ruled out for surgery and was treated with Amphotericin B and long-term Fluconazole. The presentation of Candida parapsilosis IE and subsequent imaging results of this uncommon illness are the subject of this report. This example also emphasizes the necessity of reading current clinical standards and delivering proper medical care.
Dawood Darbar, MBCHB, MD, FACC, FAHA, FHRS from the Division of Cardiology, Departments of Medicine, the University of Illinois at Chicago and Jesse Brown Veterans Administration speaks about Review Article - Genetics of atrial fibrillation—practical applications for clinical management: if not now, when and how?
Over the next few decades, the prevalence and economic burden of atrial fibrillation (AF) are expected to more than double. Early and systematic rhythm control therapy, in addition to anticoagulation and treatment of concurrent cardiovascular diseases, lowers cardiovascular outcomes when compared to a rate control strategy, favoring the safe restoration and maintenance of sinus rhythm. Antiarrhythmic medications (AADs) and catheter ablation are two current treatments for AF rhythm management (CA). Individual patient response is very varied, with some patients maintaining AF-free for lengthy periods of time on antiarrhythmic treatment while others need repeat AF ablation within weeks. The lack of effectiveness of rhythm control treatment for AF is due in part to a lack of knowledge of the pathophysiological processes and our inability to anticipate individual patient responses. As a result, determining which patients with AF are likely to react to rhythm management approaches is a huge knowledge gap. With the discovery of uncommon mutations in cardiac ion channels, signaling molecules, and myocardial structural proteins linked with familial (early-onset) AF during the last decade, great progress has been made in characterizing the genetic architecture of AF. Genome-wide association studies, on the other hand, have revealed common variations at over 100 genetic loci, and the creation of polygenic risk scores has identified people at high risk. Although retrospective studies show that common genetic variation influences response to AADs and CA, the creation of a complete clinical and genetic risk score might allow genetic data to be translated into bedside therapy for AF patients. Given the economic implications of the AF pandemic, even minor increases in treatment effectiveness might result in significant benefits for individuals and healthcare systems.