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Prakriti Gaba, MD, Cardiology Fellow at Harvard Medical School. In this video, she speaks about the Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction.

Outline

Origins:

REDUCE-IT was a double-blind experiment in which 8,179 statin-treated individuals with reduced low-density lipoprotein cholesterol and moderately increased triglycerides were randomly assigned to icosapent ethyl (IPE) or placebo. The primary objective, including death from cardiovascular (CV) causes, was significantly reduced. It was uncertain what effect IPE has on people who had previously had a myocardial infarction (MI).

Goals:

In REDUCE-IT, we wanted to look at the effect of IPE on ischemic events in patients who had previously had a MI.

Methodology:

We conducted post-hoc analysis on patients who had previously experienced MI. CV mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina were the primary endpoints. The most important secondary outcome was CV death, MI, or stroke.

Outcomes:

A total of 3,693 patients had a previous MI. With IPE vs placebo, the primary endpoint was lowered from 26.1 percent to 20.2 percent; HR: 0.74 (95 percent CI: 0.65-0.85; P = 0.00001). The main secondary endpoint was lowered from 18.0% to 13.3%; HR: 0.71 (95 percent CI: 0.61-0.84; P = 0.00006). There was also a substantial 35% relative risk reduction in total ischemia events (P = 0.0000001), 34% reduction in MI (P = 0.00009), 30% reduction in CV death (P = 0.01), and a 20% reduction in all-cause mortality (P = 0.054), despite a modest rise in atrial fibrillation. Sudden cardiac death and cardiac arrest were also drastically reduced by 40% and 56%, respectively.

Inferences:

Patients in REDUCE-IT with a history of recent MI who were treated with IPE had large and significant relative and absolute risk reductions in ischemic events, including CV mortality. (AMR101 Study to Assess Its Ability to Reduce Cardiovascular Events in High-Risk Patients With Hypertriglyceridemia and Statin Use. The primary goal is to assess the effect of 4 g/day AMR101 on the occurrence of a first major cardiovascular event. NCT01492361; [REDUCE-IT])

Prakriti Gaba, MD, Cardiology Fellow at Harvard Medical School. In this video, she speaks about the Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction.

Outline

Origins:

REDUCE-IT was a double-blind experiment in which 8,179 statin-treated individuals with reduced low-density lipoprotein cholesterol and moderately increased triglycerides were randomly assigned to icosapent ethyl (IPE) or placebo. The primary objective, including death from cardiovascular (CV) causes, was significantly reduced. It was uncertain what effect IPE has on people who had previously had a myocardial infarction (MI).

Goals:

In REDUCE-IT, we wanted to look at the effect of IPE on ischemic events in patients who had previously had a MI.

Methodology:

We conducted post-hoc analysis on patients who had previously experienced MI. CV mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina were the primary endpoints. The most important secondary outcome was CV death, MI, or stroke.

Outcomes:

A total of 3,693 patients had a previous MI. With IPE vs placebo, the primary endpoint was lowered from 26.1 percent to 20.2 percent; HR: 0.74 (95 percent CI: 0.65-0.85; P = 0.00001). The main secondary endpoint was lowered from 18.0% to 13.3%; HR: 0.71 (95 percent CI: 0.61-0.84; P = 0.00006). There was also a substantial 35% relative risk reduction in total ischemia events (P = 0.0000001), 34% reduction in MI (P = 0.00009), 30% reduction in CV death (P = 0.01), and a 20% reduction in all-cause mortality (P = 0.054), despite a modest rise in atrial fibrillation. Sudden cardiac death and cardiac arrest were also drastically reduced by 40% and 56%, respectively.

Inferences:

Patients in REDUCE-IT with a history of recent MI who were treated with IPE had large and significant relative and absolute risk reductions in ischemic events, including CV mortality. (AMR101 Study to Assess Its Ability to Reduce Cardiovascular Events in High-Risk Patients With Hypertriglyceridemia and Statin Use. The primary goal is to assess the effect of 4 g/day AMR101 on the occurrence of a first major cardiovascular event. NCT01492361; [REDUCE-IT])

Ibrahim Sultan, MD, Associate Professor of Cardiothoracic Surgery, Director, Center for Thoracic Aortic Disease, Surgical Director, Center for Heart Valve Disease, UPMC Heart and Vascular Institute at UPMC. In this video, he speaks about Transfusion of non–red blood cell blood products does not reduce survival following cardiac surgery.

Outline

Goals:

The evidence suggests that patients undergoing cardiac surgery who receive perioperative packed red blood cell (pRBC) transfusions have an increased risk of death. The current investigation is to determine whether there is a link between non–pRBC blood product transfusions and higher mortality.

Methodology:

Patients who underwent heart surgery between 2010 and 2018 were included in data from our center's Society of Thoracic Surgeons database. Patients requiring pRBC infusions or experiencing circulatory arrest were excluded. Propensity matching (1:1; caliper = 0.2 times the standard deviation of logit of propensity score) was used. Cox regression and Kaplan–Meier estimates were utilized. This study excluded individuals with cardiac transplants, ventricular assist devices, transcatheter aortic valves, and circulatory arrest.

Outcomes:

A total of 8042 patients met the analytic requirements. 395 patients requiring perioperative non–pRBC blood products (platelets, fresh-frozen plasma, and cryoprecipitate) were matched with 395 nontransfusion patients using propensity matching (1:1), resulting in equitable patient cohorts. The median duration of follow-up was 4.5 (3.0-6.4) years. Platelets (327 [82.8 percent]), fresh-frozen plasma (141 [35.7 percent]), and cryoprecipitate were given to patients (60 [15.2 percent ]). There was no statistically significant difference in postoperative mortality (6 [1.5%] vs 4 [1.0%]; P =.52). The transfusion group had higher rates of reoperation (20 [5.0 percent] vs 8 [2.0 percent]; P.02) and prolonged ventilation (36 [9.1 percent] vs 19 [4.8 percent]; P.02). Blood product use was strongly linked with emergent surgery (odds ratio [OR] 2.86 [1.72-4.78]; P.001), intra-aortic balloon pump (OR 3.24 [1.64-6.39]; P.001), and multivalve surgery (OR 4.34 [2.83-6.67]; P.001). Blood product transfusion (hazard ratio: 1.15 [0.89-1.48]; P =.3) was not related with an increased risk of death. There was no significant difference in long-term survival between groups.

Findings:

Those undergoing cardiac surgery who require blood products alone, without pRBC transfusion, have comparable postoperative and long-term survival to patients who do not require blood products. These findings are based on a small number of patients, and further research will help to improve the generalizability of these findings.

Ibrahim Sultan, MD, Associate Professor of Cardiothoracic Surgery, Director, Center for Thoracic Aortic Disease, Surgical Director, Center for Heart Valve Disease, UPMC Heart and Vascular Institute at UPMC. In this video, he speaks about Transfusion of non–red blood cell blood products does not reduce survival following cardiac surgery.

Outline

Goals:

The evidence suggests that patients undergoing cardiac surgery who receive perioperative packed red blood cell (pRBC) transfusions have an increased risk of death. The current investigation is to determine whether there is a link between non–pRBC blood product transfusions and higher mortality.

Methodology:

Patients who underwent heart surgery between 2010 and 2018 were included in data from our center's Society of Thoracic Surgeons database. Patients requiring pRBC infusions or experiencing circulatory arrest were excluded. Propensity matching (1:1; caliper = 0.2 times the standard deviation of logit of propensity score) was used. Cox regression and Kaplan–Meier estimates were utilized. This study excluded individuals with cardiac transplants, ventricular assist devices, transcatheter aortic valves, and circulatory arrest.

Outcomes:

A total of 8042 patients met the analytic requirements. 395 patients requiring perioperative non–pRBC blood products (platelets, fresh-frozen plasma, and cryoprecipitate) were matched with 395 nontransfusion patients using propensity matching (1:1), resulting in equitable patient cohorts. The median duration of follow-up was 4.5 (3.0-6.4) years. Platelets (327 [82.8 percent]), fresh-frozen plasma (141 [35.7 percent]), and cryoprecipitate were given to patients (60 [15.2 percent ]). There was no statistically significant difference in postoperative mortality (6 [1.5%] vs 4 [1.0%]; P =.52). The transfusion group had higher rates of reoperation (20 [5.0 percent] vs 8 [2.0 percent]; P.02) and prolonged ventilation (36 [9.1 percent] vs 19 [4.8 percent]; P.02). Blood product use was strongly linked with emergent surgery (odds ratio [OR] 2.86 [1.72-4.78]; P.001), intra-aortic balloon pump (OR 3.24 [1.64-6.39]; P.001), and multivalve surgery (OR 4.34 [2.83-6.67]; P.001). Blood product transfusion (hazard ratio: 1.15 [0.89-1.48]; P =.3) was not related with an increased risk of death. There was no significant difference in long-term survival between groups.

Findings:

Those undergoing cardiac surgery who require blood products alone, without pRBC transfusion, have comparable postoperative and long-term survival to patients who do not require blood products. These findings are based on a small number of patients, and further research will help to improve the generalizability of these findings.

Andrea Natale M.D., F.A.C.C., F.H.R.S., F.E.S.C., Executive Medical Director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center at Texas Cardiac Arrhythmia. In this video, he speaks about Endocardial Scar-Homogenization With vs Without Epicardial Ablation in VT Patients With Ischemic Cardiomyopathy.

Observation -

Goals:

The authors of this study compared the success of scar homogeneity with a mixed (epicarddial + endocardial) vs endocardial-only technique for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) at 5 years of follow-up.

Origins:

The best ablation strategy for achieving long-term success in VT patients with ICM is unknown.

Methodology:

Patients with ICM who underwent VT ablation at our center were divided into two groups: endocardial + epicardial scar homogenization and endocardial scar homogenization. Patients who had already undergone open heart surgery were not eligible. Despite the fact that all group 1 patients were noninducible following endocardial ablation, epicardial ablation was done. All patients received bipolar substrate mapping with conventional scar settings of >1.5 mV for normal tissue and 0.5 mV for severe scar. The procedure\'s endpoint in both groups was noninducibility of monomorphic VT. Implantable device interrogations were performed on patients every 4 months for 5 years.

Outcomes:

The study included 361 participants (n = 70 in group 1 and n = 291 in group 2). At 5 years, 81.4 percent (n = 57/70) of group 1 patients and 66.3 percent (n = 193/291) of group 2 patients were arrhythmia-free (P = 0.01). Anti-arrhythmic medications (AAD) were used by 26 of 57 (45.6 percent) and 172 of 193 (89.1 percent) of the patients in groups 1 and 2 (log-rank P 0.001). Endo-epicarddial scar homogeneity was linked with a substantial reduction in arrhythmia recurrence after controlling for age, gender, and obstructive sleep apnea (HR: 0.48; 95 percent CI: 0.27-0.86; P = 0.02).

Observations:

Despite being noninducible following endocardial ablation, epicardial substrate was found in all group 1 patients in this series of patients with ICM and VT. Furthermore, when compared to endocardial ablation alone, combined endo-epicarddial scar homogeneity was linked with a much higher success rate at 5 years of follow-up and a significantly lower demand for antiarrhythmic medicines after the treatment.

Andrea Natale M.D., F.A.C.C., F.H.R.S., F.E.S.C., Executive Medical Director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center at Texas Cardiac Arrhythmia. In this video, he speaks about Endocardial Scar-Homogenization With vs Without Epicardial Ablation in VT Patients With Ischemic Cardiomyopathy.

Observation -

Goals:

The authors of this study compared the success of scar homogeneity with a mixed (epicarddial + endocardial) vs endocardial-only technique for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) at 5 years of follow-up.

Origins:

The best ablation strategy for achieving long-term success in VT patients with ICM is unknown.

Methodology:

Patients with ICM who underwent VT ablation at our center were divided into two groups: endocardial + epicardial scar homogenization and endocardial scar homogenization. Patients who had already undergone open heart surgery were not eligible. Despite the fact that all group 1 patients were noninducible following endocardial ablation, epicardial ablation was done. All patients received bipolar substrate mapping with conventional scar settings of >1.5 mV for normal tissue and 0.5 mV for severe scar. The procedure\'s endpoint in both groups was noninducibility of monomorphic VT. Implantable device interrogations were performed on patients every 4 months for 5 years.

Outcomes:

The study included 361 participants (n = 70 in group 1 and n = 291 in group 2). At 5 years, 81.4 percent (n = 57/70) of group 1 patients and 66.3 percent (n = 193/291) of group 2 patients were arrhythmia-free (P = 0.01). Anti-arrhythmic medications (AAD) were used by 26 of 57 (45.6 percent) and 172 of 193 (89.1 percent) of the patients in groups 1 and 2 (log-rank P 0.001). Endo-epicarddial scar homogeneity was linked with a substantial reduction in arrhythmia recurrence after controlling for age, gender, and obstructive sleep apnea (HR: 0.48; 95 percent CI: 0.27-0.86; P = 0.02).

Observations:

Despite being noninducible following endocardial ablation, epicardial substrate was found in all group 1 patients in this series of patients with ICM and VT. Furthermore, when compared to endocardial ablation alone, combined endo-epicarddial scar homogeneity was linked with a much higher success rate at 5 years of follow-up and a significantly lower demand for antiarrhythmic medicines after the treatment.

Marie-Sophie de Koning, MD,  PhD Candidate in Cardiology at the UMCG Cardiology Research Institute. In this video, she speaks about AAC 2022 Abstract - Results from the GIPS-IV Trial.

Brief Synopsis:

The most effective treatment for ST-segment elevation myocardial infarction is now timely and successful reperfusion with primary percutaneous coronary intervention (PPCI) (STEMI). However, persistent myocardial injury caused by ischemia and subsequent reperfusion is seen in the vast majority of patients (88%) and poses a risk of heart failure development. In numerous experimental models, hydrogen sulfide (H2S) administration has been found to protect the heart from "ischemia reperfusion injury." Human data suggests that the H2S-releasing chemical sodium thiosulfate (STS) can be safely administered.

The goal of this study was to examine the efficacy and safety of STS versus placebo treatment on myocardial infarct size in STEMI patients treated with PCI.

A multicenter, double-blind, randomized controlled clinical trial was used for the study. A total of 380 patients aged 18 and up who were undergoing primary PCI for a first STEMI and deemed amenable by the investigator to be treated with STS 12.5g intravenously (i.v.) or matched placebo immediately after arrival at the catheterization laboratory (cath-lab) and a repeated dose administered 6 hours after the first dose, on top of standard treatment, were included in the study. The primary endpoint is the size of the infarct as determined by cardiac magnetic resonance imaging (CMR-imaging) four months following randomization.

Marie-Sophie de Koning, MD,  PhD Candidate in Cardiology at the UMCG Cardiology Research Institute. In this video, she speaks about AAC 2022 Abstract - Results from the GIPS-IV Trial.

Brief Synopsis:

The most effective treatment for ST-segment elevation myocardial infarction is now timely and successful reperfusion with primary percutaneous coronary intervention (PPCI) (STEMI). However, persistent myocardial injury caused by ischemia and subsequent reperfusion is seen in the vast majority of patients (88%) and poses a risk of heart failure development. In numerous experimental models, hydrogen sulfide (H2S) administration has been found to protect the heart from "ischemia reperfusion injury." Human data suggests that the H2S-releasing chemical sodium thiosulfate (STS) can be safely administered.

The goal of this study was to examine the efficacy and safety of STS versus placebo treatment on myocardial infarct size in STEMI patients treated with PCI.

A multicenter, double-blind, randomized controlled clinical trial was used for the study. A total of 380 patients aged 18 and up who were undergoing primary PCI for a first STEMI and deemed amenable by the investigator to be treated with STS 12.5g intravenously (i.v.) or matched placebo immediately after arrival at the catheterization laboratory (cath-lab) and a repeated dose administered 6 hours after the first dose, on top of standard treatment, were included in the study. The primary endpoint is the size of the infarct as determined by cardiac magnetic resonance imaging (CMR-imaging) four months following randomization.

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).

Link to Study:
https://www.acc.org/latest-in-cardiology/clinical-trials/2020/03/26/19/43/victoria#references-for-article

Detailed description:

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

* Concurrent

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.

Contextualization:

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.

Naveen L. Pereira, MD, Consultant for the Department of Cardiovascular Diseases and Professor of Medicine and Associate Professor of Pharmacology, Mayo Clinic College of Medicine speaks about ACC 2021 - Late-Breaking Clinic Science - Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy: A Meta-Analysis.

Link to Abstract:
https://www.jacc.org/doi/full/10.1016/j.jcin.2021.01.024

 Summary

The aim of this research was to compare the effects of ticagrelor or prasugrel versus clopidogrel treatment on clinical results in patients with coronary artery disease (CAD) who were primarily treated with percutaneous coronary intervention (PCI).

Background: The impact of CYP2C19 genotype on ticagrelor or prasugrel patient results relative to clopidogrel is unknown.

Methods: Experiments comparing the effects of CYP2C19 genotype on ischemic results during ticagrelor or prasugrel versus clopidogrel therapy were scanned through February 19, 2020. Results for CYP2C19 genotype status, clopidogrel, and alternative P2Y12 inhibitors in patients with CAD with at least 50% undergoing PCI are expected for study eligibility. The main focus of the study was on randomized controlled trials (RCTs). Non-RCTs are added to the main analysis as a supplementary analysis. Cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, and extreme chronic ischemia were the main outcomes. To analyze the two-drug regimens and assess the relationship with the CYP2C19 genotype, a meta-analysis was performed.

Seven RCTs were found among the 1,335 studies found (15,949 patients, mean age 62 years; 77 percent had PCI, 98 percent had acute coronary syndromes). The probability of prejudice was poor, and statistical variability was small. When ticagrelor and prasugrel were linked to clopidogrel, there was a substantial decrease in ischemic incidents (relative risk: 0.70; 95 percent confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 0.70; 95 percent confidence interval: 0.59 to 0.83). (relative risk: 1.0; 95 percent confidence interval: 0.80 to 1.25). The association test on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), implying that the genotype of CYP2C19 altered the effect. Four further observational experiments were discovered, and when they were used in the study, the results were the same (p-value of the interaction test 0.001).

Conclusions: The role of ticagrelor or prasugrel in minimizing ischemic events in patients with CAD who specifically experience PCI is dependent on the existence of CYP2C19 loss-of-function carrier status when opposed to clopidogrel. These findings back up genetic tests before administering P2Y12 inhibitors.

Professor of Clinical Cardiology Michiel Rienstra specializes on atrial fibrillation and heart failure. In 2009, he received a NWO Rubicon grant to pursue a post-doctoral position in population genetics and epidemiology at Harvard Medical School, Massachusetts General Hospital, and the Framingham Heart Study. In this video Dr. Rienstra speaks about Digoxin Evaluation in Chronic Heart Failure.

Link to Abstract:
https://clinicaltrials.gov/ct2/show/NCT03783429?cond=Heart&phase=23&draw=2&rank=9#contacts

Brief Synopsis:
Digoxin is the oldest and cheapest FDA-approved medication for heart failure (HF). The DIG trial, a large digoxin trial conducted in the early 1990s, found a considerable reduction in HF hospitalizations but no effect on mortality. According to a post-hoc study of the DIG trial, decreased digoxin serum concentrations may reduce not just HF hospitalizations but also mortality in chronic HF patients. A prospective, randomized, placebo-controlled trial is needed to confirm these retrospective findings and to establish digoxin's current position in the therapy of HF. As a result, the researchers want to see if low-dose digoxin, with serum concentrations of 0.5-0.9ng/mL, is useful in HF patients with low or mid-range ejection fractions (LVEF 50%).

Professor of Clinical Cardiology Michiel Rienstra specializes on atrial fibrillation and heart failure. In 2009, he received a NWO Rubicon grant to pursue a post-doctoral position in population genetics and epidemiology at Harvard Medical School, Massachusetts General Hospital, and the Framingham Heart Study. In this video Dr. Rienstra speaks about Digoxin Evaluation in Chronic Heart Failure.

Link to Abstract:
https://clinicaltrials.gov/ct2/show/NCT03783429?cond=Heart&phase=23&draw=2&rank=9#contacts

Brief Synopsis:
Digoxin is the oldest and cheapest FDA-approved medication for heart failure (HF). The DIG trial, a large digoxin trial conducted in the early 1990s, found a considerable reduction in HF hospitalizations but no effect on mortality. According to a post-hoc study of the DIG trial, decreased digoxin serum concentrations may reduce not just HF hospitalizations but also mortality in chronic HF patients. A prospective, randomized, placebo-controlled trial is needed to confirm these retrospective findings and to establish digoxin's current position in the therapy of HF. As a result, the researchers want to see if low-dose digoxin, with serum concentrations of 0.5-0.9ng/mL, is useful in HF patients with low or mid-range ejection fractions (LVEF 50%).

Professor Paul Myles, MD is the current Director of Anaesthesia and Perioperative Medicine at the Alfred and the Chair of the Academic Board of Anaesthesia and Perioperative Medicine. Professor Myles is also a Fellow of the Australian Academy of Health and Medical Sciences and an Australian NHMRC Practitioner Fellow. In this video Dr. Myles speaks about The ENIGMA II Trial: Nitrous Oxide Anesthesia and Cardiac Morbidity After Major Surgery.


Link to Abstract:
https://clinicaltrials.gov/ct2/show/study/NCT00430989?recrs=e&cond=Heart&phase=23&lupd_s=01%2F01%2F2019&lupd_e=11%2F15%2F2021&draw=3

The goal of this study was to see if nitrous oxide (N2O) anaesthesia was safe in patients who had risk factors for coronary artery disease and were having major surgery.
Description in detail:

Around 25% of individuals undergoing major surgery had known coronary artery disease (CAD) or CAD risk factors.

The metabolism of vitamin B12 and folate is disrupted by N2O. This reduces the creation of methionine (from homocysteine), which is required for the synthesis of tetrahydrofolate and thymidine in DNA. N2O anaesthesia has been shown to raise postoperative homocysteine levels on numerous occasions. Acute hyperhomocysteinaemia is known to produce endothelial dysfunction, and chronic hyperhomocysteinaemia is linked to cardiovascular disease. In one short study, patients who had N2O anaesthesia had a higher rate of postoperative myocardial ischaemia. For people with CAD who are having major surgery, reducing postoperative myocardial infarction and death are key goals.

Our earlier study (ENIGMA) looked at 2050 patients and found some major side effects, but because most of them were not at risk of CAD, we couldn't properly quantify serious cardiac problems. To offer a definitive evaluation of the safety of N2O anesthesia, we suggest a large simple randomized clinical trial with 7,000 patients.

Dr. Borge Gronne Nordestgaard is a clinical biochemist, genetic epidemiologist, educator, and Danish National Board of Health certified clinical biochemistry specialist. He received the Boserup Foundation's prize in 1994, the Quentin's Foundation's prize in 2001, and the Carlsen's Foundation's prize in 2005. In this video Dr. Nordestgaard speaks on how Elevated remnant cholesterol increases the risk of peripheral artery disease, myocardial infarction, and ischaemic stroke.

Link to Abstract:
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab705/6399975?login=true


Aims
Cholesterol in triglyceride-rich lipoproteins, also known as residue cholesterol, is increasingly recognized for its atherogenic potential. Remaining cholesterol levels are linked to a higher risk of myocardial infarction and ischemic stroke. We investigated whether high residual cholesterol is linked to an increased risk of peripheral arterial disease (PAD).

Methods and outcomes
We looked at 106 937 people from the Copenhagen General Population Study who were recruited between 2003 and 2015. 1586 people were diagnosed with PAD, 2570 with myocardial infarction, and 2762 with ischemic stroke over the course of the study, which lasted up to 15 years. We also looked at 13 974 people who were part of the Copenhagen City Heart Study in 1976–78. During the study's 43-year follow-up, 1033 people were diagnosed with PAD, 2236 with MI, and 1976 with ischemic stroke. A conventional lipid profile was used to quantify residual cholesterol. The diagnoses came from national health registries in Denmark. In the Copenhagen General Population Study, people with residual cholesterol levels of 1.5 mmol/L (58 mg/dL) vs. 0.5 mmol/L (19 mg/dL) had a multivariable adjusted hazard ratio (HR) of 4.8 (95 percent confidence interval 3.1–7.5) had a greater risk of PAD. Myocardial infarction had a score of 4.2 (2.9–6.1) and ischemic stroke had a score of 1.8 (1.4–2.5). In the Copenhagen City Heart Study, the associated HRs for PAD, myocardial infarction, and ischemic stroke were 4.9 (2.9–8.5), 2.6 (1.8–3.8), and 2.1 (1.5–3.1).

Conclusion
In the general population, elevated residual cholesterol is linked to a five-fold greater risk of PAD, which is higher than the risk of myocardial infarction and ischemic stroke.

Dr. DiDomenico, Pharm.D., BCPS-AQ Cardiology, FCCP, HFSA, FACC is an Associate Professor in the Department of Pharmacy Practice at the University of Illinois at Chicago (UIC), a member of the Center for Pharmacoepidemiology and Pharmacoeconomic Research, and a Cardiovascular Clinical Pharmacist at the University of Illinois Hospital & Health Sciences System with an inpatient cardiology practice site. In this video Dr. Dimonenico talks about Digoxin Dosing in Heart Failure: A Simplified Nomogram Versus Standard Care.

Link to Study-
https://clinicaltrials.gov/ct2/show/NCT01005602


Digoxin, a medicine used to treat heart failure, hasn't had its dose procedures updated in decades, despite recent evidence suggesting that blood levels of digoxin attained using standard dosing practices may raise the risk of adverse outcomes. We created a simple dosage method that targets lower digoxin blood levels, which have been linked to better results when compared to higher blood levels. The goal of this study is to see if this simplified dosing method is more effective in lowering blood levels than normal digoxin dosing practices, and if digoxin dosing can be further enhanced by incorporating patients' genetic information, which is thought to alter the drug's characteristics.

Digoxin is used as an additional medication in patients who have left ventricular dysfunction and symptoms of heart failure despite receiving normal treatment. Because lower serum levels in this range have been associated with improved survival whereas higher serum levels have been associated with increased mortality, the therapeutic range for digoxin in patients with heart failure has recently been redefined to a narrower therapeutic window (0.5 - 0.9 ng/ml). Dosing procedures, on the other hand, have not been modified to match the expanded digoxin therapeutic range. Using historical data, we devised a simpler digoxin dose nomogram for patients with heart failure in order to reach serum digoxin concentrations (SDC) within the revised therapeutic range. The long-term goal of this research is to prospectively confirm our digoxin dose nomogram's capacity to achieve desired SDC and give doctors with a simple tool to optimize digoxin dosing in heart failure patients. Because digoxin is a substrate of the efflux pump p-glycoprotein (pGP), and genetic polymorphisms in the MDR1 gene (which regulates pGP expression) have shown conflicting results in terms of digoxin pharmacokinetics, we'll look into the impact MDR1 functional gene variants may have on digoxin dosing. A total of 170 patients with symptomatic heart failure treated with digoxin will be included in this study, which will compare steady-state SDC in a prospective group of patients dosed according to our nomogram to a historical control group whose digoxin dose was derived from standard dosing practices. We'll also look into genetic variants in the MDR1 gene that have been linked to digoxin pharmacokinetics. The study's main goals are to compare the percentage of patients in each group who achieve steady-state SDC in the desired range of 0.5-0.9 ng/ml, characterize the relationship between genetic variability in the MDR1 gene and digoxin dosing, and update our digoxin dosing nomogram to account for the clinical and genetic variability that has been shown to have the most impact on digoxin dosing. The study's rationale is that lower digoxin doses are recommended because lower SDC is linked to better survival. In order to improve clinical outcomes and reduce the risk of adverse events, digoxin dosing regimens must be revised to reflect these recommendations and account for genetic heterogeneity of the MDR1 gene. The precise goals of this research are to address these issues:

Aim 1: Compare steady-state SDC produced with our dosing nomogram to those acquired with current dosing techniques.

Aim 2: Using our digoxin dose nomogram, characterize the link between MDR1 gene genetic diversity and SDC.

Dr. Lorenzo Gervaso works in the Division of Gastrointestinal Medical Oncology and Neuroendocrnine Tumors at the European Institute of Oncology in Milan Italy. In this video Dr. Gervaso discusses Venous and Arterial Thromboembolism in Patients With Cancer.


Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccao.2021.03.001

Abstract
In cancer patients, venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality. Myocardial infarction and stroke are common complications of arterial thromboembolism. Subgroups of people are more at risk, with greater rates of cancers such pancreatic, stomach, and multiple myeloma. Most patients with active cancer who are hospitalized for medical reasons or who have significant cancer surgery should receive thromboprophylaxis. Outpatient thromboprophylaxis is not usually suggested, but new evidence suggests that a high-risk population that may benefit from pharmaceutical thromboprophylaxis could be identified with the use of a validated risk tool. Direct oral anticoagulants are becoming the preferred new therapeutic choice for cancer-related VTE, however low-molecular-weight heparin remains the gold standard for patients with a high risk of bleeding. Management of VTE after the first six months, as well as difficult clinical conditions such as cerebral metastases and thrombocytopenia, necessitates careful consideration of the advantages and dangers of anticoagulation, and there are significant knowledge gaps in the data.
Highlights

• Patients with cancer are more likely to develop VTE and ATE, which can have serious implications, including death.
• RAMs that include clinical and biochemical characteristics can identify individuals who are at high risk.
• If a patient is diagnosed as having a high risk of VTE, thromboprophylaxis should be investigated.
• DOACs are a newer therapy option for acute VTE, however LMWH is still the gold standard.
• There is a scarcity of information on how to handle ATE in cancer patients.
• Currently, a multidisciplinary strategy involving an oncologist and a cardiologist is advised.
Introduction and Epidemiology

The link between malignancy and a clinical hypercoagulable condition has been intensively explored since it was first identified by Professor Armand Trousseau in the early nineteenth century (1), and it remains a critical public health issue for cancer patients. Thromboembolic events, such as venous thromboembolism (VTE) and arterial thromboembolism, continue to be a major concern for patients with active cancer (ATE). VTE, which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is more prevalent and can develop at any time during a cancer patient's history, and may even be the disease's first symptom (2). VTE can make surgery, hospitalizations, and systemic therapy more difficult, and it's linked to a significant increase in health-care resource consumption as compared to cancer patients who don't have VTE (3). ATEs, such as myocardial infarction (MI), cerebrovascular events (CVA), and peripheral artery disease, are important causes of death and disability around the world (4). Malignancies are not an established independent risk factor for ATE, despite the well-known changes in clotting function (5). Thromboembolism, which includes both VTE and ATE, is the second-leading cause of death in cancer patients, after the illness itself, and the incidence of thromboembolism can disrupt or delay crucial cancer treatments (6,7).

VTE rates in cancer patients are 4- to 7-fold higher than in healthy people (8), and they appear to be rising in recent years as a result of improved patient survival, more thrombogenic cancer treatments, widespread use of central catheters, and increased awareness of cancer-associated thrombosis (CAT) (9). Several clinical studies have revealed that ATEs are prevalent in cancer patients (10,11), and a prospective analysis of cancer patients undergoing outpatient chemotherapy found that arterial thrombosis was responsible for 5.6 percent of deaths (6).

The hazard ratio (HR) for VTE was 4.7 (95 percent confidence interval [CI]: 4.5 to 4.9) in a UK study comparing cancer patients to matched noncancer control people from the general population, and the incidence rate was 13.9/1,000 per year (95 percent CI: 13.4 to 14.4). (12). According to a recent study, VTE affects about 15% of cancer patients, and 20% of spontaneous VTEs represent the first indicator of an underlying malignancy (13). Navi et al. (14), who used the Surveillance, Epidemiology, and End Results (SEER) database to analyze 279,719 cancer patients (breast, lung, prostate, colorectal, bladder, pancreatic, gastric, and non-Hodgkin lymphoma) and matched them with controls between 2002 and 2011, looked at the incidence of ATE according to cancer subtypes and settings. At 6 months, the incidence of ATE was 4.7 percent in all cancer patients compared to 2.2 percent in the matched control group, however the study sample was largely older cancer patients in the United States. As a result, extrapolating the findings to other populations should be done with caution.

VTE in cancer isn't just about DVT and PE anymore, with reports of thrombosis in odd places such the upper extremities, cerebral veins, and splanchnic veins on the rise (15). With active malignancy, upper extremity thrombosis is 18 times more likely, usually due to the presence of a central venous catheter (13). Splanchnic or visceral vein thrombosis (VVT) is frequently linked to cancer, particularly specific types of gastrointestinal (GI) cancers (16). The majority of these abnormalities are detected by chance during routine surveillance or restaging scans, and their impact on prognosis and outcomes is unknown (17). ATE, on the other hand, is most commonly manifested as MI and CVA, which are far from innocuous due to their severe clinical impact.

In both the prevention and treatment of CAT, a paradigm change has occurred in recent years. New evidence suggests that individuals who take straight oral anticoagulants benefit (DOACs). For both primary and secondary prevention of thromboembolism, large trials focused on cancer populations have been undertaken. The recommended approach for both primary prevention and treatment has recently been modified by guidelines from various societies, including the American Society of Clinical Oncology (ASCO), International Society on Thrombosis and Haemostasis (ISTH), International Initiative on Thrombosis and Cancer, European Society of Medical Oncology (ESMO), National Comprehensive Cancer Network, and American Society of Hematology (ASH) (18–22).

We examine these new findings in the context of risk assessment, prevention, and treatment of both venous and arterial CAT in this review. Throughout, we looked for current data with the highest level of evidence; if it wasn't accessible, we determined that the data was derived from lower levels of evidence.

Learn more about the American College of Cardiology and what it's like to work there. #LifeAtACC

Dr. Kim Eagle provides a weekly tip for clinicians on the front lines of the COVID-19 pandemic. This week's tip provides an interim update on the Oxford COVID (ChAdOx1 nCoV-19) vaccine (https://www.acc.org/latest-in-cardiol...).

The ACC's Sandra J. Lewis Cardiovascular Women's Leadership Institute will support the unique needs of mid-career women as they continue to sustain and grow their leadership skills. Part of the ACC's Campaign for the Future, the Institute will further the College's Strategic Goals to foster a diverse pipeline of leaders within the profession and the ACC itself. "For many women, 15 to 20 years into their career, changes in responsibilities serve as an opportunity to reassess, reimagine and reinvent their professional lives," says Sandra J. Lewis, MD, FACC, whose transformational gift to the Campaign for the Future is making the Institute possible. "While this stage may serve as a professional renaissance for many, it is also a stage with opportunities for unique guidance and targeted leadership development to successfully transition forward 'to the next'.” Read more: http://bit.ly/2KefKk1 #ACCFuture #ACCWIC

Watch a COVID-19: Protecting Patients at Greatest Risk mini-course for NCD Academy on “Building Back Better to Put People First in the NCD Response: Views From Africa and the Middle East.” Learn more about the NCD Academy by visiting ACC.org/NCDAcademy.

Watch a COVID-19: Protecting Patients at Greatest Risk mini-course for NCD Academy on “Building Back Better to Put People First in the NCD Response.” Learn more about the NCD Academy by visiting ACC.org/NCDAcademy.

Watch a COVID-19: Protecting Patients at Greatest Risk mini-course for NCD Academy on “Building Back Better to Put People First in the NCD Response: Views From Asia.” Learn more about the NCD Academy by visiting ACC.org/NCDAcademy.

We discuss several of the important data coming out the American Heart Association 2020 meeting.

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We have a multispecialty panel discussion on the cardiorenal benefits of newer antidiabetic agents with Drs Rangaswami, Vaduganathan, Tuttle and Bhalla.

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We have a multispecialty panel discussion on the cardiorenal benefits of newer antidiabetic agents with Drs Rangaswami, Vaduganathan, Tuttle and Bhalla.
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We discuss several of the important data coming out the European Society of Cardiology 2020 meeting.

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We discuss cardiogenic shock and decision making in the case of a young female presenting to the ER. We have a panel of cardiologists guide the discussion. Drs Rene Alvarez, Daniel Sims and Alec Vishnevski discuss the case presented by cardiology fellow Rachna Kataria, MD.
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We discuss the various aspects of cardiogenic shock including definition, heterogeneity, classification and management with an internationally renowned expert in the field Dr Navin Kapur. Dr Kapur is the Director of the Acute Mechanical Circulatory Support Program at Tufts University School of Medicine, Boston, MA.

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Dr. Joseph Tonna, MD, MS, is a tenured Associate Professor in the Divisions of Cardiothoracic Surgery and Emergency Medicine at the University of Utah. He is the Associate Director of Extracorporeal Membrane Oxygenation (ECMO) Services, as well as the Section Head of Cardiothoracic Critical Care and Medical Director of the Cardiovascular ICU/Cardiothoracic Critical Care. His funded research program focuses on clinical trials in critically ill patients and ECMO. In this video Dr. Tonna discusses "Using ECPR During In-Hospital Cardiac Arrest (RESCUE-IHCA).

Link to Abstract
https://www.jacc.org/doi/10.1016/j.jcin.2021.09.032

Abstract
The goal of this study was to create and validate a score that could accurately predict the likelihood of death in adults who had extracorporeal cardiopulmonary resuscitation (ECPR).

Background
Although ECPR is increasingly being utilized to treat refractory in-hospital cardiac arrest (IHCA), survival rates range from 20% to 40%.

Methods
The American Heart Association's GWTG-R (Get With the Guidelines–Resuscitation) registry was used to identify adult patients who needed extracorporeal membrane oxygenation for IHCA (ECPR). To predict hospital death, a multivariate survival prediction model and score were created. The findings were externally confirmed in a different cohort of patients who had ECPR for IHCA from the Extracorporeal Life Support Organization registry.

Results
A total of 1,075 patients who received ECPR were included in the study. In both the derivation and validation cohorts, 28% of patients made it to discharge. Age, time of day, initial rhythm, history of renal insufficiency, patient type (cardiac vs noncardiac and medical vs surgical), and duration of the cardiac arrest event were all found to be associated with in-hospital death and were combined into the RESCUE-IHCA (Resuscitation Using ECPR During IHCA) score. The model exhibited adequate calibration (Hosmer and Lemeshow goodness of fit P = 0.079) and good discrimination (area under the curve: 0.719; 95 percent confidence interval: 0.680-0.757). In the external validation cohort, discrimination was reasonable (area under the curve: 0.676; 95 percent confidence interval: 0.606-0.746), and calibration was good (P = 0.66), confirming the model's ability to predict in-hospital death over a wide range of probabilities.

Conclusions
Clinicians can utilize the RESCUE-IHCA score in real time to predict in-hospital death in patients with IHCA who are receiving ECPR.

Dr. Stephane Heymans studied public health at Harvard University in Cambridge. MA and now works at Maastricht University Medical Center in the Netherlands. In this video Dr. Heymans discusses the Phenotypic clustering of dilated cardiomyopathy patients highlights important pathophysiological differences. Link to Abstract- https://academic.oup.com/eurheartj/article/42/2/162/5959816 Abstract- Dilated cardiomyopathy (DCM) is caused by a combination of hereditary and acquired factors. Until now, clinical decision-making in DCM has primarily been predicated on ejection fraction (EF) and NYHA categorization, with the DCM heterogeneity being overlooked. The goal of this work was to uncover pathophysiological differences between DCM subgroups by using phenotypic clustering to integrate aetiologies, comorbidities, and cardiac function along cardiac transcript levels. Methods and outcomes- We included 795 DCM patients from the Maastricht Cardiomyopathy Registry who were phenotyped in depth, which comprised extensive clinical data on aetiology and comorbodies, imaging, and endomyocardial biopsies. Based on unsupervised hierarchical clustering of principal components, four mutually exclusive and clinically different phenogroups (PG) were identified: [PG1] moderate systolic dysfunction, [PG2] auto-immune, [PG3] genetic and arrhythmias, and [PG4] severe systolic dysfunction. Pro-inflammatory (PG2, auto-immune), pro-fibrotic (PG3; arrhythmia), and metabolic (PG4, reduced EF) gene expression were found in cardiac samples (n = 91). Furthermore, even after accounting for well-known clinical indicators, event-free survival differed between the four phenogroups. Decision tree modeling identified four clinical parameters (autoimmune disease, EF, atrial fibrillation, and kidney function) by which every DCM patient from two independent DCM cohorts could be assigned to one of four phenogroups with corresponding outcomes (n = 789; Spain, n = 352, and Italy, n = 437), demonstrating the phenogrouping's applicability. Conclusion- The current investigation found four distinct DCM phenotypes, each with distinct clinical presentations, underlying molecular profiles, and outcomes, paving the door for a more individualized treatment approach.

Joshua D. Mitchell, MD from Washington University in St. Louis speaks about Cardiovascular Manifestations From Therapeutic Radiation: A Multidisciplinary Expert Consensus Statement From the International Cardio-Oncology Society.

Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccao.2021.06.003


Abstract
Radiation therapy is a cornerstone of cancer treatment, with more than half of patients receiving it. As a result of increased use and survival, researchers are paying more attention to the long-term effects of ionizing radiation, including cardiovascular damage. Radiation therapy can cause vascular atherosclerosis, as well as valve, cardiac, and pericardial dysfunction. The International Cardio-Oncology Society has issued a consensus statement based on broad principles of radiation treatment, cardiovascular risk assessment, and risk mitigation in this population. Anatomically based suggestions for cardiovascular management and follow-up are offered, with a focus on the early detection of atherosclerotic vascular disease on imaging to aid in the development of preventative medication. Radiation-induced cardiovascular disease has its own set of management issues, which are discussed as well. The diverse expert panel's recommendations are based on the most recent literature and constitute a unanimous consensus.
Highlights

• Radiation therapy causes valvular, myocardial, and pericardial illness, as well as other short- and long-term cardiovascular side effects in the vasculature and heart.

• Computed tomography scans used for radiation planning or cancer staging can be used to diagnose asymptomatic atherosclerosis and target preventive treatments.

• Additional practical cardiovascular disease screening suggestions based on anatomical exposure are offered.

• Radiation-induced cardiovascular disease requires special considerations, and modern percutaneous therapy is frequently favored over surgical methods.

Introduction

Since its first use in 1899, therapeutic radiation has become a cornerstone of cancer treatment, with more than half of cancer patients now receiving it (RT). RT has both short- and long-term side effects, despite its good impact on cancer outcomes and survival. RT has been related to an increased risk of long-term unfavorable cardiovascular (CV) consequences, which can lead to higher morbidity and death in cancer survivors, according to research (1-3).



Radiation-induced CV disease has a wide range of symptoms. Vascular illness (including coronary artery disease [CAD] and subclavian artery stenosis), valvular disease, constrictive pericarditis, restrictive cardiomyopathy, and heart failure (HF) are all considerably enhanced after thoracic RT. (Central Illustration). Patients are also at a greater risk of carotid artery stenosis and cerebrovascular accidents after head and neck or whole brain RT. Aorto-iliac atherosclerosis and renal artery stenosis are possible side effects of abdominal or pelvic RT. Deoxyribonucleic acid damage, oxidative stress, and the release of inflammatory and profibrotic cytokines all play a role in radiation-induced CV illness, leading to vascular, myocardial, valvular, and pericardial fibrosis.

In light of the entire context of RT benefits and hazards, doctors must be aware of CV problems and implement appropriate screening, mitigation, and prevention techniques into their practice. Although there are guidelines and expert consensus statements for detecting RT-related heart damage and dysfunction , there are few screening recommendations for extracardiac vascular symptoms. Furthermore, screening criteria for thoracic RT survivors have concentrated on the detection of obstructive CAD rather than nonobstructive CAD. This narrow focus overlooks the risk of myocardial infarction in patients with nonobstructive CAD and the importance of early medical intervention in these patients . Furthermore, newer imaging modalities such as coronary artery calcium (CAC) screening and coronary computed tomography (CT) angiography, which can more thoroughly identify a patient's CV risk during and after RT, are not included in current guidelines .

The current International Cardio-Oncology Society consensus statement systematically reviews available data and provides comprehensive recommendations for preventing, screening, diagnosing, and managing CV disease in cancer survivors receiving or who have received RT to the head and neck, chest, abdomen, and pelvis. This document discusses fundamental concepts for preventing CV illness following radiation therapy and offers recommendations for detecting specific vascular effects based on anatomical location.

The International Cardio-Oncology Society was founded in October 2019 as an international, multidisciplinary collaboration of professionals in medical oncology, radiation oncology, cardiovascular imaging, and cardio-oncology. A comprehensive literature analysis was conducted by searching the PubMed index for studies published in English from 1975 to the present, combining text words and Medical Subject Headings such as radiation, cardiotoxicity, and CV anomalies; the final search yielded 2,999 publications. The literature evaluation was completed in October 2019 and then revised before the recommendations were finalized in December 2020. We also looked for relevant titles in the references of the publications we reviewed. Evidence from randomized controlled trials or meta-analyses was given top priority, followed by well-designed nonrandomized research, other nonrandomized studies, expert opinion, and clinical experience. ClinicalTrials.gov was also used to look for any relevant clinical trials.

To study the material and provide practical recommendations, the committee met bimonthly via webinars and teleconferences. Recommendations are tagged with language like "is advised," "may be useful," and "can be considered," according to American College of Cardiology/American Heart Association consensus statements (18). Because there are few randomized controlled trials particularly designed to address CV disease in RT survivors, no levels of evidence are provided. These proposals are the result of a consensus among the members of the multidisciplinary expert committee.

Stefan Janssens, MD- 

Link to Article- https://www.jacc.org/doi/10.1016/j.jacbts.2021.07.001

• It is uncertain what role CLEC4E plays in myocardial repair following ischemia-reperfusion damage.

• Deletion of CLEC4E is linked to decreased cardiac damage, inflammation, and structural and functional remodeling of the left ventricle.

• CLEC4E is a promising target for reducing myocardial inflammation and improving ischemia-reperfusion damage repair.

Summary

C-type lectin domain family 4 member E (CLEC4E) from bacteria has a vital function in sterile inflammation, although its significance in myocardial healing is uncertain. We show that CLEC4E expression levels in the myocardium and blood correspond with the extent of myocardial injury and left ventricular (LV) functional impairment using complementary techniques in porcine, murine, and human tissues. In the ischemic heart, CLEC4E expression is dramatically enhanced in the vasculature, cardiac myocytes, and infiltrating leukocytes. A reduction in acute cardiac damage, neutrophil infiltration, and infarct size has been linked to the loss of Clec4e signaling. At 4 weeks, Clec4e–/– had considerably enhanced LV structural and functional remodeling due to reduced myocardial damage. The early transcriptome of Clec4e–/– mice LV tissue revealed considerable overexpression of transcripts involved in myocardial metabolism, radical scavenging, angiogenesis, and extracellular matrix organization compared to wild-type mice. As a result, targeting CLEC4E in the early stages of ischemia-reperfusion injury offers a prospective therapeutic method for modulating myocardial inflammation and enhancing myocardial healing.

Introduction

After a myocardial infarction, cardiac repair is a highly organized and complex series of processes that begins with an inflammatory phase marked by immune cell infiltration and the production of danger-associated molecular patterns (DAMPs) and then progresses to a reparative and proliferative phase (1-3). To allow later tissue healing and prevent maladaptive left ventricular (LV) remodeling, faulty scar formation, and poor patient outcome, the early inflammatory response with DAMPS binding to cognate pattern recognition receptors (PRRs) must be correctly and timely coordinated (4,5). Excessive or protracted inflammation causes ventricular dilatation and systolic dysfunction, increasing the likelihood of heart failure (6), whereas insufficient early inflammation fails to remove necrotic cardiac cells and matrix components, obstructing eventual tissue healing. The importance of a better understanding of the cellular and molecular pathways directing this biphasic repair process following ischemia-reperfusion (I/R) injury is highlighted by this complex and tightly regulated innate immune activation response.

Previously, we looked examined how the transcriptional profile of patients with an acute myocardial infarction (AMI) changed over time in circulating blood cells (7). We found that pro-inflammatory pattern recognition receptors, such as the C-type lectin domain family 4 member E receptor (CLEC4E), which is normally expressed on leukocytes and activated in response to bacteria, were highly activated (8,9). In vitro, this innate immune receptor detects necrotic material caused by ischemia injury (10) and suppresses the inflammatory response in experimental murine brain injury (11,12). CLEC4E's role in myocardial I/R damage, on the other hand, is uncertain.

The significance of CLEC4e signaling in the early inflammatory response and subsequent healing phase following acute myocardial ischemia injury was studied in this study, as well as its potential as a new target for intervention in myocardial I/R injury.

Methods

Ethics

The Ethics Committee for Animal Experimentation at KU Leuven (P244/2014 and P064/2017) approved all animal procedures, which were carried out in accordance with Belgian law on the care and use of experimental animals. The patient research procedure followed the Declaration of Helsinki, and all patients signed informed permission (Ethical Committee ML8525, Belgian trial no. B322201214942, S54129) (7).

I/R damage in a porcine model and cardiac magnetic resonance imaging

As previously documented, ten domestic pigs (body weight: 20-30 kg) were sedated, anesthetized, and had I/R damage by transient balloon blockage of the left anterior descending coronary artery (LAD) distal to the first diagonal branch for 50 minutes, followed by 4 hours of reperfusion (7). After 4 hours of reperfusion, a subgroup of 6 pigs underwent 3-T cardiac magnetic resonance imaging (MRI) (Prisma-Tim, Siemens) to assess infarct size (MI/left ventricle), end-systolic volume (ESV), end-diastolic volume (EDV), and ejection fraction, before being euthanized (13). Biopsy specimens were taken from the left ventricle's ischemia, border, and distant zones for differential gene expression analysis and histology. Supplementary Materials and Methods, as well as Supplementary Table 1, give more information.

I/R damage in a mouse model and cardiac MRI

Male C57Bl6/J wild-type (WT) mice aged 12 to 14 weeks were crossed with Clec4e–/– mice (031936-UCD) purchased from the Mutant Mouse Resource and Research Center. Mice were given I/R damage by ligating the LAD for 60 minutes and then reperfusing them, as described before (14). They were randomly assigned to evaluate arms with reperfusion for 24 hours (WT, n = 12; Clec4e–/–, n = 14), 72 hours (WT, n = 5; Clec4e–/–, n = 5) or 4 weeks (WT, n = 17; Clec4e–/–, n = 16). Investigators blinded to the genotype of the animals obtained cardiac MRI data on a Bruker BioSpec 70/30 7T MRI machine (Bruker BioSpin) after 4 weeks of reperfusion. Blood was taken from the inferior caval vein after euthanasia to measure high-sensitivity troponin I (hs-TnI) as a surrogate marker of cardiac injury and to isolate neutrophils to study their phenotype and migration capacity; at 24 hours after I/R injury, LV tissue was taken for histological analysis and transcriptome studies. Organs were perfused for 10 minutes with saline before being harvested for histological and differential gene expression analyses utilizing ribonucleic acid (RNA) sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). The Supplementary Materials and Methods section has more information.

The effects of Clec4e gene deletion on chemokine signaling in vitro

The Neutrophil Isolation Kit for Mice (130-097-658, Miltenyi) was used to isolate peripheral blood neutrophils from WT and Clec4e–/– mice, according to the manufacturer's instructions. WT and Clec4e–/– neutrophils were used in a transwell migration test toward a Cxcl2 gradient (10 ng/mL) to investigate the influence of Clec4e on neutrophil migration. Bone marrow cells from the femurs of WT and Clec4e–/– mice were collected to see if Clec4e changes Cxcr2 protein expression, as previously described (15). Proteins were extracted using radioimmunoprecipitation assay buffer including protease inhibitors, and Cxcr2 expression was determined using immunoblot analysis. The Supplementary Materials and Methods section has more information.

In patients with AMI, microarray CLEC4E expression was analyzed and validated with qRT-PCR.

In a profile investigation of 65 individuals with acute coronary syndrome (ACS) (GEO accession number GSE123342), CLEC4E was identified as one of the most elevated transcripts (7). We used qRT-PCR to confirm CLEC4E expression at the time of admission in 138 patients with AMI and 20 patients with stable coronary artery disease (CAD). Before discharge, CLEC4E whole blood transcript levels were compared to peak high-sensitivity troponin T (TnT) levels and LV ejection fraction.

Analytical statistics

For the number of animals studied, data are presented as mean SD or median (interquartile range). The data was analyzed blindly, and the Shapiro-Wilk and Kolmogorov-Smirnov tests were used to check for normal distributions. One-way analysis of variance (ANOVA) with Tukey's correction for multiple pairwise testing was used to examine CLEC4E expression in porcine tissue. A Kruskal-Wallis test with Dunn's adjustment for multiple comparisons was used to examine CLEC4E expression in human peripheral blood samples. For regularly distributed data, a 2-tailed Student's t-test was used, and for non-normally distributed data, a nonparametric Mann-Whitney U test was used. Two-way ANOVA with idák's correction for multiple testing was used for experiments conducted at different time points (24 and 72 hours). To investigate linear or generic connections between variables, Pearson correlations were employed for normally distributed data and Spearman correlations for non-normally distributed data, respectively. The chi-square test or Fisher exact test were used to determine categorical variable differences, which are represented by the odds ratio and 95 percent confidence intervals. Statistical significance was defined as a P value of less than 0.05. Prism version 8.0 software was used to conduct the statistical analysis (GraphPad Software).

Bertram Pitt, M.D. - @UMich @UMichCardiology #CardiovascularEvents #Cardiology #Research Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes

Link to Abstract: https://www.nejm.org/doi/full/10.1056/NEJMoa2110956?query=cardiology

`Abstract

BACKGROUND
Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has been shown to improve cardiorenal outcomes in patients with stage 3 or 4 chronic kidney disease (CKD) and significant albuminuria, as well as type 2 diabetes. Finerenone's usage in patients with type 2 diabetes and other forms of CKD is unknown.

METHODS
In this double-blind trial, patients with CKD and type 2 diabetes were randomly randomized to either finerenone or a placebo. Patients with a urinary albumin-to-creatinine ratio of 30 to less than 300 and an estimated glomerular filtration rate (eGFR) of 25 to 90 ml per minute per 1.73 m2 of body surface area (stage 2 to 4 CKD) or a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of at least 60 ml per minute per 1.73 m2 of body surface area (stage 2 to (stage 1 or 2 CKD). Patients were given renin–angiotensin system blockers that had been adjusted to the maximal dose on the manufacturer's label that did not cause unacceptable side effects before randomization. The primary outcome was a composite of mortality from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure, as measured by a time-to-event analysis. The first secondary outcome was a composite of kidney failure, a prolonged drop in eGFR of at least 40% from baseline, or death due to renal causes. Adverse occurrences reported by investigators were used to assess safety.

RESULTS A total of 7437 patients were randomly assigned to one of two groups. During a median follow-up of 3.4 years, a primary outcome event occurred in 458 of 3686 patients (12.4%) in the finerenone group and 519 of 3666 patients (14.2%) in the placebo group (hazard ratio, 0.87; 95 percent confidence interval [CI], 0.76 to 0.98; P=0.03), with the benefit driven primarily by a lower incidence of hospitalization for hepatitis C. (hazard ratio, 0.71; 95 percent CI, 0.56 to 0.90). 350 patients (9.5%) in the finerenone group and 395 (10.8%) in the placebo group experienced the secondary composite result (hazard ratio, 0.87; 95 percent CI, 0.76 to 1.01). There was no significant difference in the overall frequency of adverse events across groups. Finerenone (1.2 percent) had a greater rate of hyperkalemia-related trial regimen discontinuation than placebo (0.8 percent) (0.4 percent ).

CONCLUSIONS
Finerenone medication improved cardiovascular outcomes in patients with type 2 diabetes and stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria when compared to placebo. (Funded by Bayer; NCT02545049 on ClinicalTrials.gov for FIGARO-DKD.) (This link will open in a new tab.)

Resynchronization of the Failing Heart and Reengineering SCD Risk

Treating Dyslipidemia in 2020: Molds, Monoclonals, and mRNA Silencing

Renal Denervation Combined Carotid and Coronary Artery Disease and Critical Limb Ischemia

Lessons Learned (or Not) in Drug Development

Smooth muscle plasticity: a double-edged sword

Arjun C. Khadilkar, MD from the University of South Florida Morsani College of Medicine speaks about Cardiac Imaging and Management of Prosthetic Valve Candida Parapsilosis Endocarditis.

Link to Article:
https://www.cureus.com/articles/59959-cardiac-imaging-and-management-of-prosthetic-valve-candida-parapsilosis-endocarditis

Summary:

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.


Overview:

Fungal infective endocarditis (IE) is an uncommon and dangerous type of infective endocarditis (IE), with death rates as high as 50% [1]. Prosthetic valve implantation, cardiac implantation devices, and intravenous drug usage are all common risk factors [1]. Candida and Aspergillus species are the most frequent causative agents of fungal IE in general [1]. 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 [2]. 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 [2]. 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 [1]. 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 [1]. 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.

Conversation:

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 [3]. 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 [6]. 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 [7]. 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 [7]. In addition, for patients who are unable to undergo valve replacement, chronic long-term suppression with Fluconazole 400-800 mg daily is strongly recommended [7]. 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) [4]. In addition, 21 patients were given long-term Fluconazole maintenance treatment for an average of 13 months, with minimal side effects [4]. 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 [4]. 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.

Outcomes:

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.

Summary

We looked at the associations between plant-based diet quality and the risk of complete, ischemic, and hemorrhagic stroke to see whether a healthy plant-based diet is linked to a lower risk of stroke.

The study included 73,890 women in the Nurses' Health Study (NHS; 1984 to 2016), 92,352 women in NHSII (1991 to 2017), and 43,266 men in the Health Professionals Follow-Up Study (1986 to 2012) who were free of cardiovascular disease and cancer at the start. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI were used to assess the consistency of plant-based diets (uPDI). Participants who recorded none or less than one serving of meat or fish per month were classified as vegetarians, while those who reported more than one serving per month were classified as non-vegetarians. Ischemic and hemorrhagic strokes were classified based on medical records.

Results: A total of 6,241 stroke cases were reported during the follow-up period (including 3,015 ischemic and 853 hemorrhagic strokes). The hazard ratios (HRs) for total stroke among participants with the highest PDIs were 0.94 (95 percent confidence interval 0.86 to 1.03) for PDI, 0.90 (0.83 to 0.98) for hPDI, and 1.05 (0.96 to 1.15) for uPDI, compared to participants with the lowest PDIs. Participants with the highest hPDI had a slightly lower HR for ischemic stroke (0.92 [0.82 to 1.04]) but no stable relationships for hemorrhagic stroke. Despite the limited number of cases, we found no connection between a vegetarian diet and total stroke (1.00 [0.76 to 1.32]).

Conclusions: Those who followed a healthy plant-based diet had a lower risk of total stroke.

JACC: Case Reports Editor-in-Chief Dr. Julia Grapsa is joined by Deputy Editor Dr. Eric Bates, Associate Editors Drs. David Fischman and Mladen Vidovich, and a panel of other experts including Drs. George Dangas, Ajay Kirtane, and Poonam Velagapudi. The panel discusses a selection of newly published cases from the January 2021 issue that focus on interesting procedural complications. Please visit https://www.jacc.org/ and https://www.acc.org/ for more information.

JACC: Case Reports Editor-in-Chief Dr. Julia Grapsa is joined by Associate Editor Dr. Maurizio Taramasso, co-host Dr. Ana Paula Tagliari, and other experts Drs. Francesco Maisano, Bernard Prendergast, Tiffany Patterson, Simon Redwood. The panel discusses a selection of newly published cases from the January 2021 issue and focus on cases that present interesting structural complications. Please visit https://www.jacc.org/ and https://www.acc.org/ for more information. 

JACC: Case Reports Editor-in-Chief Dr. Julia Grapsa is joined by Editorial Consultant Yevgeniy “Eugene” Brailovsky; authors Drs. Mohammad Sarraf, Daniel Burkhoff, and Michael I. Brener; as well as Prof. Nicolas van Mieghem from Erasmus University to discuss a case reporting the first-in-man description of pressure–volume analysis in all four cardiac chambers before and after transcatheter aortic valve replacement. Pressure–volume analysis demonstrated that the hemodynamic consequences of valve replacement are chamber-specific and influenced by all aspects of the procedure (i.e., rapid ventricular pacing), not just valve deployment. #JACCCardioOnc Please visit https://www.jacc.org/ and https://www.acc.org/

Journal Editor-in-Chief Bonnie Ky, MD, MSCE, FACC, moderates a video case presentation on Early Immune Checkpoint Inhibitor Cardiotoxicity presented by Han Zhu, MD, with associate editor discussants Dan Lenihan, MD, FACC; Ana Barac, MD, PhD, FACC; Ronald Witteles, MD, FACC; and Anne Blaes, MD. The experts discuss two newly published manuscripts related to the topic, “The Evolving Immunotherapy Landscape and the Epidemiology, Diagnosis, and Management of Cardiotoxicity,” by Lili Zhang, MD, ScM and Tomas G. Neilan, MD, MPH et al., and the French Working Group’s Viewpoint on “Management of Immune Checkpoint Inhibitor-Induced Myocarditis: Plea for a Pragmatic Approach,” led by Franck Thuny, MD, PhD, et al. Please visit https://www.jacc.org/ and https://www.acc.org/ for more information

Maurice Sarano, MD of the Minneapolis Heart Institute speaks about STS 2021 Discussion - STS/CSCS: Tricuspid Valve Surgery Associated with Left Sided Cardiac Disease: When, What, and How?

Link to Abstract -
https://www.eventscribe.net/2021/STS/fsPopup.asp?efp=SEJKWElTSFExMjA3NA&PresentationID=815982&rnd=0.2613683&mode=sessionInfo


Diagnosis and treatment of tricuspid regurgitation associated with left-sided heart disease are difficult. A multidisciplinary group of experts will discuss the natural history of tricuspid regurgitation, diagnosis, and surgical and transcatheter management in this session.

Learning Goals:

Explain the natural history of left-side cardiac disease-related tricuspid regurgitation and its prognostic implications

Recognize tricuspid valve care timing and indications

Describe tricuspid regurgitation surgical and transcatheter therapies