Coverage of the annual AHA Scientific Sessions

AHA Scientific Sessions 2020

A new study from Thomas Jefferson University is providing evidence in support of their prediction model for determining risk of stroke and other cardiovascular complications in patients undergoing non-cardiac surgery.

Results of the study indicate the web-based model could help identify patients at high-risk for these events and allow clinicians the ability to circumvent this risk when possible.

"Often times we do the research and publish a research paper that is too complex to translate to the bedside," said lead investigator Sang Woo, MD, director of the Division of Hospital Medicine at Thomas Jefferson University, 

. "My goal from the beginning was to come up with a new model that is very practical and useful and that can be incorporated into routine patient care."

Despite advances in technology and monitoring, cardiovascular complications following non-cardiac surgery remain a significant risk for many. With this in mind, the current study was designed as a way to validate a prediction model developed by Woo and a team of colleagues from Thomas Jefferson to assess risk for these events.

Woo and team designed their model using data from the Universal American College of Surgeons National Surgical Quality Improvement Program (ACS‐NSQIP). Specifically, the model was developed based on a cohort of 809,880 patients treated between 2007-2009. The model was created using information related to the age, history of coronary artery disease, history of stroke, emergency surgery, preoperative serum sodium, creatinine, hematocrit, American Society of Anesthesiologists physical status class, and type of surgery. This model was subsequently tested using ACS-NSQIP data from 2010.

The primary outcomes of interest for the study were postoperative 30-day stroke, major cardiovascular events, and 30-day mortality. For the purpose of analysis, major cardiovascular events included myocardial infarction, cardiac arrest, or stroke.

In the cohort of 355,870 patients from 2010 used to test the model, major cardiac complications occurred in 0.66% (n=5332) of patients (myocardial infarction, 0.28%; cardiac arrest, 0.41%), postoperative stroke occurred in in 0.25% (n=2005), and 30‐day mortality was 1.66% (n=13,484). Upon analysis, result indicated the risk prediction model had high predictive accuracy with area under the receiver operating characteristic curve for stroke (training cohort=0.869, validation cohort=0.876), major cardiovascular events (training cohort=0.871, validation cohort=0.868), and 30‐day mortality (training cohort=0.922, validation cohort=0.925).

Further analysis indicated surgery types, history of stroke, and coronary artery disease appeared to be significant risk factors for stroke and major cardiac complications. The surgery types associated with highest risk of stroke were vascular (thoracic‐EVAR), brain surgery, and carotid endarterectomy. For cardiac complications, procedures associated with greatest risk were open aorta surgery, thoracic‐EVAR, suprainguinal bypass, intestinal surgery, and liver/pancreas/spleen surgery.

“Using 9 clinical variables in a national cohort of patient data from the robust ACS‐NSQIP database collected over 4 years, we developed and validated a clinically useful risk assessment model for stroke, cardiac, and mortality risk,” wrote investigators in their conclusion.

Development and Validation of a Prediction Model for Stroke, Cardiac, and Mortality Risk After Non‐Cardiac Surgery,

Journal of the American Heart Association.

Articles

A web-based model developed by a team at Thomas Jefferson University appeared to accurately predict risk of stroke and adverse cardiovascular events following non-cardiac surgery. 

Web-Based Model Shows Promise for Predicting Stroke, Cardiac Events after Non-Cardiac Surgery

Results of a modeling study by investigators at Tufts University suggest nearly two-thirds of all COVID-19 hospitalizations can be attributed to the presence of four specific preexisting conditions.

An analysis that included data from more than 900,000 COVID-19 hospitalizations, results indicate 64% of hospitalizations were attributable to obesity, hypertension, diabetes, and 

—with more than 30% of all hospitalizations attributable to obesity alone.

"While newly authorized COVID-19 vaccines will eventually reduce infections, we have a long way to go to get to that point. Our findings call for interventions to determine whether improving cardiometabolic health will reduce hospitalizations, morbidity, and health care strains from COVID-19," said Dariush Mozaffarian, MD, DrPH, lead investigator and dean of the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University, 

. "We know that changes in diet quality alone, even without weight loss, rapidly improve metabolic health within just six to eight weeks. It's crucial to test such lifestyle approaches for reducing severe COVID-19 infections, both for this pandemic and future pandemics likely to come."

With previous observational studies linking the aforementioned cardiometabolic conditions to increased risk of severe outcomes with COVID-19, Mozaffarian and colleagues from the Friedman School sought to assess absolute and proportional COVID-19 hospitalizations attributable to each condition, jointly and separately, and according to race/ethnicity, age, and sex. Designed as a comparative risk assessment, investigators chose the NHANES 2015-2018 for cardiometabolic conditions and Centers for Disease Control and Prevention’s Coronavirus Disease 2019–Associated Hospitalization Surveillance Network (COVID-NET) database and from the COVID Tracking Project for COVID-19 hospitalizations as data sources for their study.

Investigators identified a total of 906,849 hospitalizations for COVID-19 among US adults that had occurred as of November 18, 2020. When assessing the proportion of hospitalizations attributable to each disease separately, results of the model indicated 274,322 (30.2%) were attributable to obesity, 237,738 (26.2%) were attributable to 

, 185,678 (20.5%) were attributable to diabetes, and 106,139 (11.7.%) were attributable to heart failure. When assessing the conditions jointly, results indicated the four conditions accounted for 575,419 (63.5%) of the 906,849 hospitalizations. Investigators pointed out further analysis suggested 10% reductions in national prevalence rates of each condition could have prevented approximately 11% of COVID-19 hospitalizations.

Like many previous studies, the investigators’ analysis also revealed disparities in COVID-19 attributable to these conditions based age and race/ethnicity. Specific disparities highlighted within the study included age-based disparities in hospitalizations attributable to diabetes and increased attributability to all four conditions among Black adults than White adults. Investigators also noted some disparities appeared to become greater when combing age and race/ethnicity into comparative models.

"Medical providers should educate patients who may be at risk for severe COVID-19 and consider promoting preventive lifestyle measures, such as improved dietary quality and physical activity, to improve overall cardiometabolic health. It's also important for providers to be aware of the health disparities people with these conditions often face," said first investigator Meghan O'Hearn, a doctoral candidate at the Friedman School, in the aforementioned statement.

Investigators cautioned clinicians to consider limitations within their study before overinterpreting the results. These limitations included inability to prove causation and the inability to prove improvements will reduce risk of COVID-19 hospitalization.

Coronavirus Disease 2019 Hospitalizations Attributable to Cardiometabolic Conditions in the United States: A Comparative Risk Assessment Analysis

An analysis using data from the CDC, COVID-NET, and the COVID Tracking Project suggests nearly 2 out of 3 COVID-19 hospitalizations in the US were attributable to obesity, hypertension, diabetes, and heart failure. 

AHA Study Links 4 Major Conditions to More than 60% of COVID-19 Hospitalizations

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New research from the University of Pittsburgh suggests women with hypertensive disorders of pregnancy should undergo regular cardiovascular screenings, even if they are not showing symptoms of cardiovascular disease.

An analysis of data from 132 women suggests women with a history of hypertensive disorders of pregnancy had notable differences in left ventricular structure and function a decade after pregnancy.

"Hypertension is a silent killer," said lead investigator Malamo Countouris, MD, a clinical instructor in cardiology at Pitt's Department of Medicine and a co-director of the UPMC Magee-Womens Hospital Postpartum Hypertension Clinic, 

 "None of the women in our study had clinical symptoms of heart disease—they are young and probably feel well and healthy, and may not be seeing a health care provider regularly—but it's important to start screening them for high blood pressure early."

Led by Countouris, a team from the University of Pittsburgh sought to examine the long-term effects of hypertensive disorders of pregnancy on cardiac remodeling. To do so, investigators designed their study as an analysis of data from women identified within the Magee Obstetric Maternal and Infant database from the University of Pittsburgh. From the database, investigators obtained information related to medical history of women with pregnancies delivered from 2008-2009. These women were then asked to take part in an additional; visit between 2017-2019 where they underwent transthoracic echocardiograms and assessments ofheight, weight, and blood pressure by standardized methods.

In total, investigators identified 132 women for inclusion in their study. Of these, 102 had normotensive pregnancies and 30 had hypertensive digs-orders of pregnancy, including 21 with pre-eclampsia and 9 with gestational hypertension. The overall cohort was 10±1 years removed from delivery and had a mean age of 39±6 years. Of the women with pre-eclampisa, 6 had severe pre-eclampsia and 7 experienced a pre-term delivery.

Upon analysis, those with hypertensive disorders of pregnancy during their index pregnancy were more likely to have current hypertension at 8-10 years after delivery compared to their counterparts without hypertensive disorders of pregnancy when measured according to visit blood pressure or antihypertensive medication use (63.3% vs 25.5%; 

<.0001). Additionally, women with hypertensive disorders of pregnancy were more likely to have diabetes (20.7% vs 7.0%; 

=.03), higher systolic blood pressure (125±12 mmHg vs 114±13 mmHg; 

 <.0001), higher diastolic blood pressure (82 ±10 mmHg vs 74±9 mmHg; 

 <.0001), and there appeared to be a trend toward a higher proportion of placental maternal vascular malperfusion (MVM) lesions (63.3% vs 45.1%; 

After adjustment for race, age, MVM lesions, BMI, current hypertension, and HbA1c, women with a history of hypertensive disorders of pregnancy had greater inter ventricular septal thickness and relative wall thickness then those with normotensive pregnancies. Further analysis indicated both a history of hypertensive disorders of pregnancy and current hypertension had greater portions of left ventricular remodeling compared to all other groups. Additionally, investigators noted these patients also had lower mitral inflow E/A ratio and annular e’.

"Identifying women at high risk can provide a window of opportunity for targeted interventions to prevent heart disease," said Countouris. "Suggesting simple changes in lifestyle or diet, including regular exercise and better management of other cardiovascular risk factors, can prevent adverse changes in the heart and lower the risk of heart disease later in life."

Association of Hypertensive Disorders of Pregnancy With Left Ventricular Remodeling Later in Life

Journal of the American College of Cardiology.

An analysis of data from 130 women suggests those with hypertensive disorders of pregnancy were at an increased risk of cardiovascular disease later in life, even if they had no baseline history of cardiovascular disease.

Hypertension in Pregnancy Predicts Cardiovascular Disease Risk A Decade After Birth

An analysis of data from a major women’s health study is underlining the impact of increased consumption of plant protein on risk of death, 

, and dementia-related death among older women.

Funded by the National Institutes of Health and National Heart, Lung, and Blood Institute, results of the study provide valuable insight to clinicians and add to the ongoing conversations surrounding dietary science and nutrition.

"Our findings support the need to consider dietary protein sources in future dietary guidelines," said study lead investigator Wei Bao, MD, PhD, an assistant professor of epidemiology at the University of Iowa in Iowa City, in a 

statement from the American Heart Association

. "Current dietary guidelines mainly focus on the total amount of protein, and our findings show that there may be different health influences associated with different types of protein foods."

Despite an almost innumerable number of studies examining plant versus animal protein and other sources of nutrition, debate still exists surrounding the effectiveness of increased protein from either source on overall, but particularly, cardiovascular health. For the purpose of their study, investigators designed their analysis to use data from postmenopausal women enrolled in the Women’s Health Initiative from 1993-1998 and followed through February 2017.

Of the 142,267 women considered eligible for inclusion in the current study, 137,481 had information related to a valid food frequency questionnaire. From this group, investigators excluded 137 with missing data on postmenopausal hormone therapy use, 24,427 who had a history of cardiovascular disease at baseline, and 10,366 women with a history of cancer at baseline. In total, 102,521 women were selected for inclusion.

During 1,876,205 person-years of follow-up, a total of 25,976 deaths occurred, including 6993 from cardiovascular disease, 7516 from cancer, and 2734 from dementia. Specific causes of cardiovascular disease included 776 from definite coronary heart disease, 1808 from cerebrovascular disease, 140 from pulmonary embolism, 2120 from possible coronary heart disease and 2149 from other or unknown cardiovascular diseases. The most common form of cancer among those who died included lung cancer, breast cancer, and pancreatic cancer. Based on results of validated FFQ responses, investigators categorized patients into quintiles based on the consumption of various forms of protein reported.

When comparing the highest quintile of plant protein consumption to the lowest, consumption of plant protein was inversely associated with all-cause mortality (HR, 0.91; 95% CI, 0.86-0.96), cardiovascular disease mortality (HR, 0.88; 95% CI, 0.79-0.97), and dementia mortality (HR, 0.79; 95% CI, 0.67-0.94).

When assessing other major protein sources, those in the highest quintile of consuming processed red meat (HR, 1.06; 95% CI, 1.01-1.10) and consuming eggs (HR, 1.14; 95% CI, 1.10-1.19) was associated with increased risk of all-cause mortality. Additionally, analyses indicated being in the highest quintile for consumption unprocessed red meat(HR, 1.12; 95% CI, 1.02-1.23), eggs (HR, 1.24; 95% CI, 1.4-1.34), or dairy products (HR, 1.11; 95% CI, 1.02-1.22) was associated with greater risk of cardiovascular disease mortality. Further analysis also revealed egg consumption was associated with a higher risk of cancer mortality (HR, 1.10; 95% CI, 1.02-1.19).

When evaluating dementia mortality, investigators found processed red meat was associated with a greater risk of dementia mortality while consumption of poultry was associated with a lower risk. Investigators also highlighted a substitution analysis suggested substituting animal protein with plant protein was associated with a lower risk of all‐cause mortality, cardiovascular disease mortality, and dementia mortality. Furthermore, this same analysis suggested substitution of total red meat, eggs, or dairy products with nuts was associated with a lower risk of all‐cause mortality.

“It is important to note that dietary proteins are not consumed in isolation, so the interpretation of these findings could be challenging and should be based on consideration of the overall diet including different cooking methods,” said study investigator Yangbo Sun, MD, PhD, a postdoctoral research scholar at the University of Iowa in Iowa City and assistant professor of epidemiology at the University of Tennessee Health Science Center, in the aforementioned statement.

Association of Major Dietary Protein Sources With All‐Cause and Cause‐Specific Mortality: Prospective Cohort Study

Using data from the Women's Health Initiative, a new analysis found increased intake of plant protein was linked to lower risk of all-cause mortality, as well as deaths related to cardiovascular disease and dementia, in postmenopausal women. 

Plant Protein Intake Linked to Lower Risk of All-Cause, Cardiovascular Death Among Aging Women

New research from an analysis of data within the STS/ACC Transcatheter Valve Therapy (TVT) Registry is questioning the effectiveness of cerebral embolic protection devices (EPDs) for mitigating stroke risk during transcatheter aortic valve replacement (TAVR).

While a secondary, propensity-matched analysis indicated an 18% lower odds of in-hospital stroke with EPD use, results of the primary analysis suggested EPD use resulted in an absolute difference of -0.15%, which led investigators to call for larger, randomized trials to assess safety and efficacy of use in TAVR patients.

“These findings provide a strong basis for large-scale randomized controlled trials to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR,” wrote investigators. “More definitive data from ongoing randomized trials powered to detect differences in clinically-important endpoints are necessary to support use of EPDs in TAVR.”

Despite advances in techniques and technology, stroke remains a serious and persistent risk following TAVR. With this in mind, a team led by David Cohen, MD, director of Clinical and Outcomes Research of the Cardiovascular Research Foundation, sought to assess how use of EPDs might influence in-hospital stroke risk using data from the STS/ACC TVT Registry.

For the purpose of analysis, investigators included adults aged 18 years and older who underwent elective or urgent TAVR from January 2018-December 2019 for native aortic valve disease or a degenerated surgical bioprosthesis. Exclusion criteria for the study included undergoing TAVR at a surgery performing 20 or fewer procedures annually, repeat TAVR procedures, undergoing TAVR via non-transfemoral access, and missing data, among others.

In total, investigators identified 123,186 patients from 599 sites for inclusion in their study. Overall, use of EPD during TAVR increased over time, with rates of usage peaking in 2019 with use at 28% of sites and 13% of TAVR procedures. Investigators noted wide variation in EPD use across the sites included in the study with 8% of sites representing more than 50% of EPD use and 72% of sites reporting no EPD use.

The primary outcome of the analysis was in-hospital stroke. Investigators also included other events such as in-hospital stroke or death, 30-day stroke, and 30-day mortality. For the purpose of analysis, stroke was defined as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction. Of note, investigators designed their study to include an instrumental variable analysis, which was used as the primary analysis, and a propensity scored-based secondary analysis using overlap weighting.

In their primary analysis, which used an instrumental variable model, there was no association between EPD use and in-hospital stroke ([adjusted relative risk, 0.90 [95% CI, 0.68-1.13], absolute risk difference: -0.15% [95% CI, -0.49 to 0.20]). In a secondary analysis using a propensity-score based model results suggested EPD use was associated with 18% lower odds of in-hospital stroke (adjusted OR 0.82 [95% CI, 0.69-0.97], absolute risk difference -0.28% [95% CI: -0.52 to -0.03]). This secondary analysis also suggested EPD use was associated with a lower risk of in-hospital stroke or death, 30-day stroke, and 30-day mortality.

Cerebral Embolic Protection and Outcomes of Transcatheter Aortic Valve Replacement: Results from the TVT Registry,

An observational analysis of data from more than 120k patients provides an overview of cerebral embolic protection devices and risk of in-hospital stroke among patients undergoing TAVR. 

Analysis of STS/ACC TVT Registry Indicate EPD Use May Not Protect Against Stroke 

Reflecting on a Year of COVID-19 in Critical Care Cardiology

Slideshows

Dr. Gregory Weiss offers his thoughts on the most clinically impactful studies related to COVID-19 and cardiology released in the past year from his perspective as a critical care cardiologist. 

One Year of COVID-19: A Critical Care Cardiologist's Review

New insights from a 12-week trial of middle-aged and older men on testosterone therapy suggest testosterone therapy has no beneficial effect on vascular health or function.

While some have theorized testosterone therapy could counteract the effects of aging on arteries, results of the trial indicate improvements in artery health and function were linked to increased physical activity and not testosterone therapy.

"The global increase in testosterone use has been very large, particularly among middle-aged and older men who might see it as a restorative hormone to increase energy and vitality," said lead investigator Daniel J. Green, PhD, Winthrop Professor and cardiovascular exercise physiology researcher in the School of Human Sciences at The University of Western Australia in Perth, 

. "However, previous studies are mixed as to whether replacement testosterone is beneficial or not, or whether it provides additional benefit over and above the effects of an exercise program."

With an interest in further understanding the effects of testosterone therapy in aging men, Green and a team of colleagues designed the current study to assess the impact of testosterone versus exercise training on endothelium-dependent flow-mediated dilation percentage and endothelium-independent glyceryl trinitrate percent responses. Designed as a 2x2 factorial randomized controlled trial, the 12-week study enrolled 80 men between 50-70 years of age with a waist girth of 95 centimeters or more and low to normal serum testosterone levels.

In total, 78 patients were included in the final analysis and underwent randomization. Of these 78, 21 were randomized to topical testosterone and a strutted exercise program, 18 were randomized to testosterone with no exercise, 20 were randomized to placebo therapy and no exercise, and 19 were randomized to placebo therapy with exercise. Of note, those randomized to testosterone therapy received 5% testosterone cream.

Investigators pointed out prescreening questionnaires allowed for the exclusion of patients based on smoking status, history of cardiovascular disease, and other factors. Additional inclusion criteria included having a fasting serum total testosterone of 6-14 nmol/L, a total cholesterol of 7 mmol/L or more, and a minimum eGFR of 45 ml/min.

Upon analysis, results indicated serum testosterone levels increased beyond 14 nmol/L among 62% of those randomized to testosterone therapy. Results also indicated exercise training was associated with increased flow-mediated dilation percent (

=.033; testosterone and exercise: +0.5, placebo and exercise: +1.0 versus testosterone and no additional exercise: −0.7, placebo and no additional exercise: +0.2%), while this effect was not apparent among those receiving testosterone therapy and it was not additive to exercise (

Additionally, there were no significant exercise or drug main effects on glyceryl trinitrate responses (

 >.05). Further analysis suggested exercise training was associated with improved endothelium-dependent vasodilator function, but testosterone therapy did not appear to influence flow-mediated dilation percent or add to the benefit of exercise. Investigators highlighted vascular smooth muscle sensitivity to nitric oxide was not modified by exercise, testosterone, or their combination.

“The results of our study suggest that if you are a healthy but relatively inactive middle-aged or older man with increased abdominal girth, and you are worried about your risk of heart attack, stroke or diabetes, then an exercise program with some support and supervision can help to improve the function and health of your arteries,” Green said. “Testosterone therapy may have some benefits, for example in increasing muscle mass in the legs, however, we didn’t find any benefits in terms of artery function, which is a determinant of future cardiovascular risk.”

Testosterone and Exercise in Middle-to-Older Aged Men

Analysis of data from a 12-week study by investigators in Australia suggests testosterone therapy was not associated with improvements in arterial health or function. 

Exercise, Not Testosterone Therapy Can Improve Vascular Function in Aging Men 

New research from Northwestern Medicine suggests the cardiovascular health of a mother during her first pregnancy could offer insight into the long-term health of her children.

An analysis of more than 2000 mother-child pairs indicates 

 at 28 weeks’ gestation, which was assessed based on BMI, blood pressure, and other factors, can help predict offspring 

"Our new findings suggest that the children of this large group of mothers with suboptimal cardiovascular health may be at higher risk for early declines in their own cardiovascular health during childhood," said lead investigator Amanda Perak, MD, assistant professor of pediatrics and preventive medicine at Lurie Children's Hospital and Northwestern University Feinberg School of Medicine, 

. "If we can address these underlying causes of children's poor heart health, we can hopefully help them avoid future heart attacks, strokes and premature deaths as they grow up."

Using data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and HAPO Follow-up study, Perak and a team of colleagues from Northwestern and Lurie Children’s Hospital designed their study with the hope of assessing how maternal cardiovascular health during pregnancy might be associated with offspring cardiovascular health in adolescence. From the studies, investigators identified a cohort of 2302 mother-child dyads from 9 centers in multiple countries for inclusion. Of note, this represents 48% of the HAPO Follow-up study population.

For the purpose of analysis, cardiovascular health was assessed according to 5 metrics: BMI, blood pressure, total cholesterol levels, glucose level, and smoking status. Mothers underwent assessments of each of these metrics at 28 weeks’ gestation. For their offspring, investigators assessed cardiovascular health using 4 metrics: BMI, blood pressure, total cholesterol levels, and glucose level, which were assessed between the ages of 10-14 years. Scores for mothers ranged from 0-10 and scores for offspring ranged from 0-8.

From the HAPO studies, investigators obtained disinformation related to maternal demographics, parity, and alcohol use through patient questionnaires. Additionally, maternal gestational age was determined by last menstrual period or an ultrasound. All of these factors were used as covariates in fully-adjusted analysis.

Among the dyads included in the study, mothers had a mean age of 29.6 (SD, 2.7) years and children had a mean age of 11.3 (SD, 1.1) years. During pregnancy, mothers had a mean maternal cardiovascular health score of 8.6 out of 10.

Upon analysis, 32.8% of pregnant mothers had metrics considered ideal, but 6.0% had 2 or more poor metrics and the distribution of cardiovascular health categories among offspring varied according to maternal cardiovascular health category. In adjusted models, results indicated women with worse maternal cardiovascular health, which was defined as having 2 or more poor metrics, had a greater relative risk of having offspring with 1 (RR, 2.02; 95% CI, 1.55-2.64) and 2 or more (RR, 7.82; 95% CI, 4.12-14.85) poor metrics when compared to mothers with ideal metrics.

In fully-adjusted models, which accounted for birth factors including preeclampsia, did not fully explain significant associations observed in the other analyses. Specifically, results indicated children born to mothers with 2 or more poor metrics during pregnancy were at a 6.23-fold increase in risk of having 2 or more poor metrics at follow-up (RR, 6.23; 95% CI, 3.03-12.82).

"Our study combined multiple factors across a range of levels, and found that the associations of maternal cardiovascular health with offspring cardiovascular health were not driven by any one metric (such as obesity)," Perak added. "Instead, all metrics were related to the offspring's later health."

Associations of Maternal Cardiovascular Health in Pregnancy With Offspring Cardiovascular Health in Early Adolescence

An analysis of more than 2k mother-child dyads suggests assessments of cardiovascular health could provide insight into the health of offspring during adolescence. 

Mother's Heart Health Sheds Light on Offspring Health in Adolescence 

A new observational study is challenging the results of the ISCHEMIA trial after returning results suggests an invasive approach may be more effective for patient patients with anatomically high‐risk stable ischemic heart disease.

While ISCHEMIA concluded an early invasive approach did not provide substantial benefit in patients with stable ischemic heart disease, investigators noted the study did not address the effect of left main disease and high-risk coronary anatomy, which was the aim of the current study.

"What our results are saying is that medical management is important, but there might be a small group that would benefit from revascularization, and we need to find ways to identify that group of patients," said lead investigator Kevin Bainey, MD, director of the Adult Cardiac Catheterization and Interventional Cardiology Laboratory and the Interventional Cardiology Fellowship Program, 

. "The main message I want clinicians to know is that it's important to know the anatomy.”

To fill the apparent gap in knowledge related to effectiveness of optimal medical therapy compared to early invasive intervention in patients at a high anatomical risk coronary anatomy, Bainey and a team of colleagues designed their current study as an observational analysis using data from the APPROACH registry. From this cohort, investigators identified 9016 patients with stable ischemic heart disease and high-risk coronary anatomy.

For inclusion in the current study, patients were required to have 3 vessel disease with 70% or greater stenosis in all 3 epicardial vessels or left main disease with 50% or greater stenosis. Investigators noted these patients were all treated between April 1, 2002 and March 31, 2016. Investigators also created subgroups of interest for angiographic risk, which were defined as 3 vessel disease with 1 vessel stenosis of 95% or greater, 3 vessel disease with proximal left anterior descending coronary artery (pLAD) with 70% or greater stenosis, 3 vessel disease with pLAD and 95% or greater stenosis, left main disease with 50% or greater stenosis, and severe left main with 70% or greater stenosis.

For the purpose of analysis, investigators established a primary composite outcome of all-cause death or myocardial infarction in patients receiving revascularization versus conservative management with optimal medical therapy.

Upon analysis, investigators found 61% (n=5487) of patients received revascularization with either coronary artery bypass graft surgery (n=3312) or percutaneous coronary intervention (n=2175) and 39% (n=3529) were managed conservatively. Results indicated undergoing coronary revascularization was associated with a reduction in the study’s primary composite outcomewhen compared with section for conservative management (Inverse Probability Weighted hazard ratio [IPW‐HR]; 0.62; 95% CI, 0.58-0.66; 

<0.001; IPW‐HR 0.57; 95% CI 0.53-0.61; 

<.001, respectively). Further analysis suggested a similar risk reduction occurred when examining percutaneous coronary intervention (IPW‐HR, 0.64; 95% CI, 0.59-0.70, 

<.001) and coronary artery bypass grafting (IPW‐HR, 0.61; 95% CI, 0.57-0.66; 

"We strongly believe coronary anatomy is an important prognostic indicator of health outcomes," added Bainey. “In a patient who has a higher-risk stress test and is showing symptoms, we think it's valuable to perform a coronary angiogram to get a complete picture, rather than just managing them with medications."

Long‐Term Clinical Outcomes Following Revascularization in High‐Risk Coronary Anatomy Patients With Stable Ischemic Heart Disease

An analysis of data from the APPROACH registry suggest early revascularization with CABG or PCI may be a more effective approach than medical therapy in patients with stable ischemic heart disease and high-risk cardiac anatomy.

Early Revascularization More Effective than Conservative Approach in Patients with High-Risk Cardiac Anatomy

A recent study from clinicians in London is sounding the alarm on the potential for damage to the heart as a result of contracting coronavirus disease 2019 (COVID-19).

An analysis of MRI data more than 140 patients discharged from acute care hospitals, results indicate about half of the patients hospitalized with severe COVID-19 with increased troponin levels appeared to suffer from subsequent cardiovascular issues in the following months, with infarction, myocarditis, ischemia, and combinations of all 3 appearing in this patient population.

“Importantly, the pattern of damage to the heart was variable, suggesting that the heart is at risk of different types of injury,” said Marianna Fontana, MD, lead investigator and a professor of cardiology at University College London, 

. “While we detected only a small amount of ongoing injury, we saw injury to the heart that was present even when the heart's pumping function was not impaired and might not have been picked up by other techniques. In the most severe cases, there are concerns that this injury may increase the risks of heart failure in the future, but more work is needed to investigate this further.”

With previous studies suggesting severe COVID-19 could have lingering effects on cardiovascular health and those with pre-existing cardiovascular conditions at an increased risk of severe outcomes during an infection, Fontana and a team of colleagues designed the current study to assess the potential for myocardial injury in recovered patients. With this in mind, investigators designed their study as an analysis of patients treated at 6 different London-area hospitals.

For inclusion in the analysis, patients needed to be discharged before June 20, 2020, have a confirmed diagnosis of COVID-19, and have undergone multi-parametric cardiovascular magnetic resonance (CMR) at least 1 month after discharge from the hospital. Additionally, patients were required to have elevated troponin levels, which was defined as hsTnT greater than 14 ng/L for females or greater than 34 ng/L for men, depending on the hospital.

In total, investigators identified 148 patients for inclusion in their analysis. The mean age of this group was 64±12 years, 70% were men, 32% required ventilatory support, and the median time after discharge to CMR was 68 days.

Upon analysis, investigators found patients had a mean LVEF of 89% (67±11%). Results also indicated late gadolinium enhancement or ischemia was observed in 80 of the 148 patients included in the study. Specifically, a myocarditis-like scar was seen in 39 patients, infarction or ischemia was noted in 32 patients, and the presence of both was observed in a group of 9 patients.

When assessing myocarditis-like injuries, investigators pointed out injury was limited to 3 or less myocardial segments in 35 of 40 cases and there was no observed left ventricular dysfunction observed. Additionally, investigators noted 30% of these patients had active myocarditis. Investigators found myocardial infarction in 28 of the 148 patients and inducible ischemia in 20 of 76 with data related to adenosine stress perfusion.

Among portents with an observed ischemic injury pattern (n=41), none of them had a past history of coronary artery disease. Furthermore, investigators noted there was no evidence of diffuse fibrosis or edema in the remote myocardium when comparing COVID-19 patients to matched controls treated prior to January 1, 2020.

"These findings give us two opportunities: firstly, to find ways of preventing the injury in the first place, and from some of the patterns we have seen, blood clotting may be playing a role, for which we have potential treatments. Secondly, detecting the consequences of injury during convalescence may identify subjects who would benefit from specific supporting drug treatments to protect heart function over time,” added Fontana.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance

An analysis of nearly 150 patients with severe COVID-19 and increased troponin levels indicates more than half of those patients went on to develop infarction, myocarditis, ischemia, or a combination of the three. 

More than 50% of Severe COVID-19 Patients Develop Subsequent Heart Damage

You respond to a code blue for a man in his 70’s who is waiting for SNF placement after recent admission for COVID-19. His COVID tests are now negative and his symptoms have resolved. The nurses were readjusting his position in bed when he suddenly collapsed and became unresponsive. An AED was attached and read “No Shock Advised”. 

A monitor was attached about two minutes later and showed asystole. CPR is in progress and 2 rounds of Epi have been given. You ask the nurse if anything has been different today prior to the arrest and she mentions that his legs look a bit swollen today and his urine output has decreased.

: GCS = 3, minimal respiratory effort being bagged. You call for a pulse check and note a rhythm in the 30’s with a decent pulse. BP is measured and is 95/55.

Computer Read: Atrial fibrillation with slow ventricular response, RBBB, rate = 30, QTc = 332.

Check out our latest case report from Brady Pregerson, MD, which features a man in his 70s who recently recovered from COVID-19. Can you determine the correct diagnosis?

Case Report: Code Blue and Leg Edema

In a historic move, the US Food and Drug Administration (FDA) has expanded the indication of sacubitril/valsartan (Entresto) to include reducing the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure—making sacubitril/valsartan the first and only therapy approved to treat heart failure patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), according to a 

The approval comes just two months after a 12-to-1 vote by the FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) in favor of a new indication for sacubitril/valsartan based on the results of the PARAGON-HF, PARAMOUNT, and PARADIGM-HF trials.

“This approval is a significant advancement, providing a treatment to many patients who were not eligible for treatment before because their ejection fraction was above the region we normally considered reduced. Until now, treatment for these patients was largely empiric,” said Scott Solomon, MD, Professor of Medicine at Harvard Medical School and Brigham and Women's Hospital, and PARAGON-HF Executive Committee Co-Chair, in the aforementioned statement. “We can now offer a treatment to a wider range of patients who have an LVEF below normal.”

With previous approvals for the treatment of patients with HFrEF dating back to 2014, the label expansion means sacubitril/valsartan has the potential to be included in treatment algorithms for approximately 5 million patients. According to the aforementioned statement from Novartis, the label expansion was based on efficacy and safety evidence from within the PARAGON-HF trial.

A phase 3 trial enrolling 4822 patients with an ejection fraction of 45% or greater, PARAGON-HF compared sacubitril/valsartan (97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (160 mg twice daily). Despite not meeting its primary endpoint, results of the trial indicate the angiotensin receptor-neprilysin inhibitor (ARNI) fell just short of proving statistical significance for reducing heart failure hospitalizations and death in HFpEF patients with a 

“We are proud of our goal to reimagine medicine. This commitment has enabled us to bring Entresto to millions more heart failure patients in the US, many of whom did not have an approved treatment option until now,” said Marie-France Tschudin, President, Novartis Pharmaceuticals. “This achievement would not have been possible without tremendous dedication from investigators, patients in our clinical trials, and the advocacy community, to whom we are extremely grateful.”

For further insight into the use of sacubitril/valsartan for treating patients with HFpEF, check out this video from PARALLAX lead investigator Burkert Pieske, MD, professor of medicine and director of cardiology at Charite University Medicine, from ESC 2020.

Novartis announced the US FDA has expanded the label for sacubitril/valsartan (Entresto) to include reducing the risk of CV death and hospitalizations for heart failure among patients with chronic heart failure. 

FDA Expands Label for Sacubitril/Valsartan (Entresto) to Include Some HFpEF Patients

He was the greatest medical scientist of his time. But Rudolph Virchow, a German pathologist of the 19th century, was very perplexed. He saw more people who had died from some type of yellow “gruel” inside of the arteries of the heart, the aorta, and the legs. Virchow called this mysterious process “arteriosclerosis,” and he ruminated that the yellow material came from the human diet.

The smoldering suspicion that the material clogging arteries was from the diet remained for another 50 years, as the chemists dissected the molecular structure of the gruel, first called cholesterin and then cholesterol. The conundrum became more perplexing; cholesterol was already known to be a crucial “backbone” molecule of the membranes of every cell in the human body, especially for the nerves. Why was this essential component of life causing such catastrophic disease?

The answer would need to wait more decades. The bedrock belief that the diet was the cause came in the early 20th century; the impact of genetics ever later. The work of the scientist who confirmed the “diet hypothesis” remained hidden to Western medicine until the mid-20th century. In 1912, a young researcher named Nikolai Anichkov in St. Petersburg fed Russian rabbits various types of food—protein, fat, pure cholesterol, and carbohydrates. With meticulous science he proved that diet caused the process that was by then called “atherosclerosis.”

The main culprit was not fat in general; the cause was the cholesterol. Although cholesterol was vital to manufacturing cells, somehow the cholesterol that wasn’t needed was ending up inside of arteries. To this day, most doctors and scientists still don’t know Anichkov’s name.

The events of the last century, two disastrous conflicts, economic depression, and then a “cold war” between Soviet Russia and the West, shut down much of the scientific interchange of many nations. A nuclear physicist, inspired by the death of his father from a heart attack, resurrected Anichkov’s work in the late 1940’s, and took the old findings much further. John Gofman, MD, PhD, a man who had worked on the Manhattan Project to develop the nuclear bomb, knew how to use a unique machine at the time: a high-speed centrifuge.

Gofman knew much more about cholesterol by then. Its particular scaffolding of molecules made it challenging for the body to absorb. It didn’t mix with water, and it’s H20 that lords over all of the molecular traffic of the human body. Evolution needed to be clever. Once cholesterol entered the intestine, it was met with by a welcoming crew of protein molecules, ready to latch on to the cholesterol molecules and wrap them up into packages of several different types. Since cholesterol is a form of fat or lipid, it was logical to call these combination particles “lipoproteins.”

The lipoproteins came in different sizes, and Gofman knew that they had a variety of weights of their molecules. He had great success using his centrifuge to spin at high-speed raw uranium to separate out the tiny amounts of the radioactive atoms. Why couldn’t his machine do the same thing to the lipoproteins in the blood of humans?

Within a few years, Gofman separated the various types of lipoproteins by how they layered out in a tube after centrifugation. Of these specific lipoproteins, now four types named based on their “density,” might one be the specific cause of atherosclerosis? Through scrupulous work, both in the laboratory and using the blood of people with coronary artery disease, Gofman was convinced that it was just one of the lipoproteins that was the culprit agent of atherosclerosis. It was the low-density lipoprotein, the “LDL” molecule.

As groundbreaking as Gofman’s work was, how LDL got into the body, and then into the liver, the body’s manufacturing plant of molecules, was still shrouded. Gofman suspected that diet was a main driver of the body’s inability to deal with too much cholesterol intake. He was one of the first physicians to point the finger at the Western diet of too much animal fat and carbohydrates as a major cause of the “heart attack epidemic” of the mid-20th century.

Gofman was not alone in studying cholesterol and atherosclerosis by the 1950’s. The intricate metabolism of cholesterol was being elucidated, discovering that it was one particle liver enzyme that was “rate-limiting,” and ultimately determined that organ’s production of cholesterol.It had the tongue-twisting name of hydroxymethylglutaryl-coenzyme reductase; for “short” -HMG coenzyme reductase.

Still, the secrecy of how cholesterol was trafficked remained. The liver can make its own cholesterol but how does it deal with the diet’s contribution? It was two very sick children seeking help at the National Institute of Health in the late 1960’s that inspired two nascent researchers to crack the “cholesterol code.” These unfortunates had already suffered heart attacks and were not even ten years old.

Michael Brown and Joseph Goldstein were training to become metabolism scientists at the NIH, and were also spending a few hours a week seeing patients in a clinic. Goldstein was assigned the care of these two youngsters, discovering that their blood had hideously high levels of LDL cholesterol, undoubtedly the cause of their premature coronary artery atherosclerosis. He also knew that for his patients, eating too much cholesterol was not the cause of their malady. This disease was a genetic one, a fate determined by the DNA of their birth.

Goldstein knew that he had no therapy to offer the children, and shared his frustration with his close friend Brown. They set their skills to work to figure out the inherited metabolic disorder in these people in their laboratory. Within only a few years, the two had identified a particular molecule on the outer surface of cells that shepherd the LDL particle into the cell, and that in their two young patients, like the rare others with this genetic disease, had “LDL receptors” that were much fewer in number, or not present at all, unlike normal people. The cholesterol-laden LDL particles entering their body had no place to land, other than the wall of arteries resulting in atherosclerosis and heart attacks.

Brown and Goldstein were awarded the Nobel Prize in Medicine in 1985 for their discoveries, and combined with the understanding of the entire metabolism of cholesterol and LDL, led to the miraculous medications that are now used to prevent atherosclerosis and save lives, in people who have already suffered a myocardial infarction, and millions of others who are at risk of this often devastating disease. The foundation of basic science has led to the translation of difficult and intellectually trying work to rescuing so many from the heart attack epidemic.

The future is bright for more understanding and treatment options to blunt, and perhaps eradicate, the scourge of atherosclerosis. It is vital that the doctors and researchers of the present and the future understand the scientific underpinnings of how they treat patients every day.

a cardiologist based in the Greater Philadelphia area focused in adult congenital heart disease, interventional cardiology, and preventive medicine

Meshkov is also the author of the forthcoming book 

Chasing the Widowmaker: The Story Behind the Century-Long Battle to Vanquish the Heart Attack Pandemic

With a backdrop of American Heart Month, Arnold Meshkov, MD, reflects on the history of cholesterol and advances in the treatment of cholesterol disorders throughout history.

The Cholesterol Odyssey with Arnold Meshkov, MD

A new study from investigators in Germany suggests creation and implementation of specialized mobile stroke units could have a dramatic impact on global function following a 

While the city of Berlin has been using these mobile units, called STEMOs (Stroke-Einsatz-Mobile), for years, results of the nonrandomized, the intervention trial indicates patients for whom these units were dispatched experienced higher rates of survival without long-term disability than their counterparts receiving standard care.

"In our study, dispatch of a mobile stroke unit was linked to increased survival and reduced risk of disability," said senior investigator Heinrich Audebert, MD, Professor in the department of neurology and Center for Stroke Research at Charité – Universitätsmedizin Berlin, 

. “The relative odds of these patients having significant disabilities three months after stroke was 29 percent lower than in patients cared for by the conventional emergency medical services. STEMO dispatch therefore results in significantly more stroke patients returning to an independent life after stroke."

Developed in conjunction with the Berlin Fire Department, the mobile stroke units were launched in February 2011 with the aim of providing diagnosis and treatment procedures to stroke patients in a more timely manner. Of note, these mobile units are sent in addition to a conventional ambulance, not as a replacement for these vehicles.

Designed to bring necessary tools and instruments to patients sooner after a stroke event, mobile stroke units were equipped with a CT scanner and the ability to perform point-of-care laboratory testing and thrombolysis. and staffed by a paramedic, a radiology technician with emergency training, and a neurologist with training in emergency medicine.

In an effort to demonstrate the effects of implementing similar interventions, investigators designed their study as a prospective, nonrandomized, controlled intervention study and conducted from February 1, 2017 through October 30, 2019. As per study design, emergency dispatchers simultaneously dispatched a mobile stroke unit and ambulance. If a mobile stroke unit was not available, these patients were identified as controls for the investigators’ analysis.

The primary outcome of the study was the distribution of modified Rankin Scale (mRS) scores at 3 months. Additionally, investigators included a 3-tier disability scale at 3 months as a coprimary outcome.

In total, 1543 patients were identified for included in the primary analysis, including 749 who received care from a mobile stroke unit and 794 who received care from a conventional ambulance. The mean age of the study cohort was 74 years and 47% were women. Additionally, 87% had available mRS scores and 98% had information available related to the 3-tier disability scale assessment.

Upon analysis, patients with a mobile stroke unit dispatched had lower median mRS scores at month 3 (3; IQR, 0-3) than their counterparts without a mobile stroke unit dispatched (2; IQR, 0-3) (OR, 0.71; 95% CI, 0.58-0.86; 

Furthermore, patients who had a mobile stroke unit dispatched had lower 3-month coprimary disability score. In comparison, more patients who had no to moderate disability in the mobile stroke unit group (80.3% vs 78%) while fewer patients had severe disability or died (7.1% vs 8.8%). Investigator noted this translated to a 27% lower odds of a worse functional outcome when a mobile stroke unit was dispatched (OR, 0.73; 95% CI, 0.54-0.99; 

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin

An intervention trial from Germany suggests specialized mobile stroke units could help improve rates of disability and death following a stroke. 

Specialized Mobile Stroke Units Decreased Risk of Long-Term Disability

Patients who exercise less are more likely to suffer a fatal heart attack, according to a new study from investigators in Europe.

A pooled analysis of data from 10 cohort studies examining myocardial infarction, results of the study indicate patients with lower levels of physical activity were at an increased risk of death during the acute phase of a myocardial infarction.

"Almost 18% of patients with a heart attack died within 28 days, substantiating the severity of this condition. We found an immediate survival benefit of prior physical activity in the setting of a heart attack, a benefit which seemed preserved at 28 days,” said Kim Wadt Hansen, MD, PhD, lead investigator and postdoctoral research fellow from the Department of Cardiology at Bispebjerg Hospital in Denmark, 

With an interest in further assessment of the cardioprotective effects of physical activity, investigators sought to explore how physical activity levels might influence risk of death following myocardial infarction. To do so, investigators designed their study as a collaborative pooled analysis of European observational cohorts including patients with a baseline assessment of physical activity, conventional risk factors, and follow-up on myocardial infarction and death.

In total, investigators invited 17 cohort studies to contribute data for analysis. After exclusion of nonrespondents and those with insufficient data, 10 studies were identified for inclusion in the pooled analysis. These 10 studies were conducted across a multitude of European nations, including Denmark, the Netherlands, Greece, and the United Kingdom, and contained data related to 1,495,254 individuals. Among this patient population, 28,140 individuals developed an incident myocardial infarction during follow-up and these individuals were included in the investigators’ final analysis.

For the purpose of analysis, investigators created 4 groups to classify levels of physical activity among participants—sedentary, low, moderate, and high. The criteria for placement into these groups were defined as less than 7 metabolic equivalents (MET)-hours per week, 7-16 MET-hours per week, 16.1-32 MET-hours per week, and more than 32 MET-hours per week, respectively.

Of the 28,140 patients included in the final analyses, 4976 (17.7%) died within 28 days of their incident myocardial infarction. Upon analysis, results indicated 62.3% (n=3101) of these events were classified as an instant fatal myocardial infarction.

In comparison to sedentary individuals, those reporting higher levels of physical activity had lower adjusted odds of instant fatal myocardial infraction, with decreased odds for those with low (OR, 0.79; 95% CI, 0.60-1.04), moderate (OR, 0.67; 95% CI, 0.51-0.89), and high (OR, 0.55; 95% CI, 0.40-0.76) physical activity levels. Additionally, similar results were observed when assessing for 28-day fatal myocardial infarction, with decreased odds for low (OR, 0.85; 95% CI, 0.71-1.03), moderate (OR, 0.64; 95% CI 0.51-0.80), and high (OR, 0.72; 95% CI, 0.51-1.00) physical activity levels.

Investigators noted a low-to-moderate degree of heterogeneity was observed in the analysis of instant fatal myocardial infarction (

=47.3%) but not in the analysis of 28-day fatal myocardial infarction (

=0.0%). Investigators also cautioned against over-interpretation of results based on multiple limitations within their study, which included the observational nature of design and potential bias in misclassification of events, among others.

"Based on our analyses, even a low amount of leisure-time physical activity may in fact be beneficial against fatal heart attacks, but statistical uncertainty precludes us from drawing any firm conclusions on that point,” added Hansen.

Association of fatal myocardial infarction with past level of physical activity: a pooled analysis of cohort studies

An analysis of more than 28k incident myocardial infarction events demonstrates increased physical activity levels were associated with a 21-45% lower risk of instant death and a 15-36% lower risk of death in the first 28 days. 