European Society of Cardiology Congress 2021

Patrick Campbell is the senior editor of Practical Cardiology, as well as its sister publication Endocrinology Network. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. In his free time, he enjoys traveling, sports, and exploring the great outdoors. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

The US FDA’s label expansion for sacubitril/valsartan (Entresto) in February 2021 could increase the potential patient population by nearly 2 million patients and prevent or postpone up to 180,000 heart failure events with comprehensive implementation, according to the results of a new study.

A decision analytical model study using data from NHANES, the GWTG-HF registry, and PARAGON-HF, results provide clinicians with insight into the newly eligible patient population outlined in the FDA’s label expansion for patients with 

“We undertook this analysis to really study a range of ejection fractions that may define what below normal may mean and how that may influence the potential population who may be eligible for use of sacubitril/valsartan, as well as the potential benefits we may see in clinical practice with the full implementation of this therapy,” said Muthiah Vaduganathan, MD, MPH, cardiologist at Brigham and Women’s Hospital and lead investigator of the study, in an interview with 

 creating uncertainty around the specific ejection fraction range considered appropriate, Vaduganathan and a team of colleagues from multiples institutions in the US and abroad sought to provide clinicians with an overview of the potential impact of optimal implementation based on a range of ejection fractions. The study was designed to use data from the National Health and Nutrition Examination Survey (NHANES) from 2015-2018 and left ventricular ejection fraction (LVEF) distribution data from the Get With The Guidelines-Heart Failure (GWTG-HF) registry to quantify newly eligible candidates and apply treatment effects observed in PARAGON-HF to assess the impact of implementation.

While the trial failed to meet its primary end point, PARAGON-HF provided valuable insight into the treatment effects of sacubitril/valsartan among patients with an ejection fraction of 45% or greater. Briefly, the PARAGON-HF trial concluded the 3-year number-needed-to-treat (NNT) was 20 for heart failure hospitalizations, 19 for total heart failure hospitalizations and cardiovascular death, and 17 for worsening heart failure events and cardiovascular death.

From NHANES, investigators identified 19,255 patients with self-reported heart failure, which investigators noted correlates to an estimated patient population of 5,604,076 (95% CI, 4,674,944-6,533,208). From the GWTG-HF registry, investigators obtained data related to LVEF measurements for 559,520 patients. Of these, 45.4%, which correlates to an estimated 2,124,182 individuals, would have already been considered eligible for sacubitril/valsartan prior to the February 2021 label expansion.

Results of the investigators analysis suggested the new FDA label for sacubitril/valsartan could expand the patient population by 643,161 (95% CI, 534,433-751,888) when below normal was considered 41-50% and by 1,838,756 (95% CI, 1,527,911-2,149,601) when below normal was considered 41-60%. Based on the treatment effects observed in PARAGON-HF, investigators estimated comprehensive implementation could prevent up to 69,268 (95% CI, 57,558-80,978) worsening heart failure events using the 41-50% definition of below normal and 182,592 (95% CI, 151,725-213,460) using the 41-60% definition.

“Our estimates are likely over-optimistic in that many of those patients who may be eligible and may stand to benefit may, in fact, ultimately go untreated. So, this does provide that optimistic estimate, however, as perhaps a goalpost that, as a community, if we were to achieve this degree of implementation, these are the potential resultant averted hospitalizations and averted worsening heart failure events that we may be able to achieve,” Vaduganathan added.

, Clyde Yancy, MD, MSc, chief of cardiology at Northwestern Medicine and deputy editor of 

 provides perspective on the need for therapies in HFpEF and explores what he describes as the “evolution of the FDA evidence bar”. 

“The urgency of need for effective therapies for HFpEF cannot be discounted, and it is likely that sacubitril/valsartan is a new therapy for certain patients with HFpEF. Clinical implementation will resolve any residual uncertainties and will test the integrity of this evolved FDA evidence bar,” wrote Yancy. “Unfailingly, the correct approach remains further discovery science, but for now, a new, reasonably evidence-based therapy in HFpEF emerges, and for those patients with both the morbidity and mortality risks of HFpEF, hope is palpable.”

Potential Implications of Expanded US Food and Drug Administration Labeling for Sacubitril/Valsartan in the US

Articles

An analysis leveraging data from NHANES, the GWTG-HF registry, and PARAGON-HF is providing insight into the potential impact of the FDA's expanded label for sacubitril/valsartan based on optimal implementation.

Sacubitril/Valsartan Label Expansion Could Increase Patient Base by Nearly 2 Million 

The US Food and Drug Administration (FDA) has approved the Portico with FlexNav transcatheter aortic valve replacement (TAVR) system for use in patients with symptomatic, severe aortic stenosis considered to be at high or extreme risk for open-heart surgery.

 on September 20, the approval is based on results of the PORTICO IDE trial and, according to Abbott, allows the company to offer the industry’s most comprehensive portfolio of solutions to structural heart disease in the US.

"For people in the U.S. suffering from aortic stenosis and unable to have surgery, the Portico with FlexNav system offers a safe and effective treatment option," said Raj Makkar, MD, associate director of Interventional Technologies at Cedars-Sinai's Smidt Heart Institute and co-principal investigator of the PORTICO IDE trial, in the aforementioned statement.

Regarded as one of the most significant advances in cardiology in recent decades, TAVR provides patients with aortic stenosis with a less invasive alternative to surgical aortic valve replacement. According to Abbott, Portico is a self-expanding TAVR valve with intra-annular leaflets and is designed to be implanted with the FlexNav delivery system.

The PORTICO IDE trial was designed as a prospective multicenter, noninferiority, randomized controlled trial enrolling patients from 52 medical centers in the US and Australia and randomizing them in a 1:1 ratio to TAVR with the first-generation Portico valve and delivery system or another commercially available valve. The trial randomized 750 patients who were aged 21 years or older, in New York Heart Association (NYHA) functional class II or higher, and had severe native aortic stenosis. The study arms included 381 randomized to the Portico valve and 369 to commercially available valves.

The primary safety end point of the trial was a composite of all-cause mortality, stroke, bleeds requiring transfusion, acute kidney injury requiring dialysis, or major vascular complications at 30 days. The primary efficacy end point was all-cause mortality or dialing stroke at 1 year. Investigators followed patients to assess clinical outcomes and valve performance up to 2 years following the procedure.

Upon analysis, results of the trial indicated the event rate was higher with the Portico valve than in the commercial valve group at 30 days (13.8% vs 9.6%; absolute difference: 4.2 [95% CI, −0.4 to 8.8]; UCB, 8·1%; 

 for superiority=.071). For the primary efficacy end point, results suggested rates were similar between the study arms with an event occurring among 14.8% in the Portico arm and 13.4% in the commercial valve arm (difference: 1.5% [95% CI, −3.6 to 6.5]; UCB, 5.7%; 

 for superiority=.50). When assessing outcomes at 2 years, rates of death (22.3% vs 20.2%; 

=.40) or disabling stroke (3.1% vs 5.0%; 

=.23) were similar between the Portico and commercial valve arms.

"With the approval of our TAVR therapy in the US, physicians now have access to an even more robust set of solutions to treat structural heart disease," said Michael Dale, senior vice president of Abbott's structural heart business. "This latest and important introduction of Portico with FlexNav represents another milestone in our work to advance our mission to restore health and improve quality of life so more people can get back to living fuller lives."

On September 20, Abbott announced the FDA had approved their Portico with FlexNav TAVR system for patients with symptomatic, severe aortic stenosis based on results of the PORTICO IDE Trial. 

FDA Approves Portico with FlexNav TAVR System from Abbott

This article was originally published on 


A review of the latest European Society of Cardiology (ESC) Prevention Guidelines at The Metabolic Institute of America (TMIOA) 2021 Heart in Diabetes sessions in New York, NY this weekend provided insight into European experts’ valuation of tools designed to stratify long-term cardiovascular risk in patients.

Presented by Kausik Ray, MBChB, MD, MPhil, Professor of Public Health and Honorary Consultant Cardiology at Imperial College London, the review highlighted ESC’s implementation of the SCORE2 and SCORE-OP algorithms—the former designed to estimate 10-year risk of cardiovascular disease and the latter designed to estimate older patients’ cardiovascular risk by 4 geographical risk regions in Europe.

The presentation also highlighted the SMART risk tool, designed to provide relative risk for patients nearing thresholds of cardiovascular intervention.

 at the TMIOA meeting, Ray discussed these new tools and their role in better interpreting cardiovascular risk in under-treated populations—namely, women and younger patients.

“For primary prevention, we’ve got healthcare systems by and large that are geared up for treating disease rather than preserving health,” Ray explained. “One of the issues with primary prevention is that the vast majority of events that are going to occur will actually occur in that group, because there’s many more of these in absolute terms.”

As Ray explained, younger patients are generally susceptible to nonfatal cardiovascular events that generally don’t register as surpassing the treatment threshold, and women similarly are treated less for their cardiovascular risks than male counterparts. SCORE2 provides perspective on both fatal and nonfatal events, as well as gender disparities in risk, he said.

“It’s trying to match care to level of risk. You don’t want to overtreat low-risk people,” Ray said. “If we can speak the language of risk, we can speak the language of benefit.”

Videos

Professor Kausik Ray provides perspective on the most recent cardiovascular disease prevention guidelines debuted by the European Society of Cardiology at ESC Congress 2021.

ESC Prevention Guidelines, With Kausik Ray, MBChB, MD, MPhil

Data from an ancillary study of the CONNECT-HF trial provide support for use of digital tools in an effort to improve management and outcomes among adult patients with heart failure.

Presented at the Heart Failure Society of America 2021 Annual Scientific Meeting, results of the study demonstrate patients using the had greater improvements in optimizing medication adherence and had a lower risk of heart failure rehospitalization or all-cause mortality, but investigators noted this reduction did not reach statistical significance.

“CONNECT-HF was the first large multicenter trial to implement mobile health technology in longitudinal care following hospitalizations for heart failure,” said Adam DeVore, MD, MHS, assistant professor of medicine at Duke University School of Medicine, 

 “As digital health technologies evolve, future work must also understand how best to engage different groups of patients while reducing risks of expanding health disparities through digital technology use.”

CONNECT-HF was a cluster-randomized clinical trial was conducted from 2017-2020 at 161 US hospitals and included 5647 patients. With primary composite end point of heart failure hospitalization or all-cause mortality, the trial compared the effects of a quality improvement intervention versus usual care among patients hospitalized with heart failure with reduced ejection fraction (HFrEF). Upon conclusion of the trial, results suggested there were no significant difference in the primary end point based on whether a patient received the intervention or were randomized to usual care.

As part of the original CONNECT-HF trial, hospitals randomized to the digital intervention early were able to enroll in an optional ancillary study assessing the effects of using a mobile health application from HealthStar. Of the 5647 patients enrolled in the study, 2431 were offered digital tools at discharge from the hospital. The digital intervention included a self-guided program designed to track and improve adherence to medication, activity recommendations, diet, and weight measurements over a 12-month period. During his presentation Vishal Rao, MD, MPH, of Duke University School of Medicine, pointed out some versions of the app included features testing loss aversion, accountability, and negatively framed incentives.

Using data from the 1276 patients offered digital tools, investigators identified matched cohorts of 310 digital tool users to 310 nonusers from the usual care group according to age, sex, site, and number of eligible quality metrics at baseline. Although matched cohorts were used, Rao pointed out there were no significant differences in baseline characteristics or medication use between those who used the digital tool and those who declined the digital tool among those in the intervention arm of the trial.

Rao also made note of declines in use of the digital tools among users—pointing out use declined to 68% by 4 weeks and below 30% by week 52. However, Rao noted the industry standard for commercial health application use around 14% at 1 year.

Upon analysis, results indicated digital users experienced greater increases in the composite heart failure quality score compared to nonusers, with a between-group difference of 4.3%, which increased to 4.9% (3.32-6.57; 

=.0025) after adjustment for baseline composite score. The primary composite outcome occurred among 41.4% of nonusers and 36.7% among digital users, which correlated to a 16% reduction in relative risk (HR, 0.84 [95% CI, 0.65-1.07]; 

“This study shows promise that a digital tool such as a mobile app could help patients improve the care they administer at home and out of the hospital,” Rao said. “This warrants further study, but digital tools could be a key to improved personalized care as we partner with patients and empower them to help improve their quality of life.”

The Association Of Digital Tool Use And Heart Failure Care: Insights From The Connect-hf Trial

Data from the CONNECT-HF trial from HFSA 2021 suggest use of a digital tool designed to improve adherence could contribute to improving outcomes among patients discharged from the hospital with heart failure with reduced ejection fraction. 

Digital Apps Could Improve Outcomes, Adherence Among Patients With Heart Failure


SGLT2 inhibitors have made major headlines in recent years with revelations of their cardiorenal protective benefits, but endocrinologists and cardiologists alike have pointed out use agents within the class does not provide a reduction in risk of stroke.

The topic of the role of diabetes medications in stroke prevention was the focus of a discussion led by Silvio Inzucchi, MD, professor of medicine at the Yale School of Medicine, at The Metabolic Institute of America’s (TMIOA) 2021 Heart in Diabetes sessions in New York, NY. During his discussion, Inzucchi provided an overview of the effects of newer diabetes medications on stroke but also touched upon potential reductions observed with more entrenched staples of diabetes management.

After his presentation at Heart in Diabetes, our sister publication 

 sat down with Inzucchi for more insight into his presentation and the role of diabetes medications in stroke prevention.

After presenting at TMIOA's 5th Heart in Diabetes meeting, Silvio Inzucchi, MD, reviews current knowledge related to the effects of diabetes medications on stroke risk. 

Diabetes Medications and Stroke Prevention, With Silvio Inzucchi, MD

Data from a phase 2 clinical trial presented at the Heart Failure Society of America 2021 Annual Scientific Meeting suggests use of aficamten could improve functional capacity in patients with obstructive hypertrophic cardiomyopathy.

A novel, second-generation selective cardiac myosin inhibitor being evaluated as an oral drug therapy, results of the REDWOOD-HCM trial suggest aficatem was well-tolerated and use resulted in the elimination resting left ventricular (LV) outflow tract gradients among 93% of the trial’s high-dose cohort. Investigators also pointed out use of aficamten associated with reductions in NT-proBNP.

“Results from REDWOOD-HCM underscore the potential clinical utility of aficamten based on the elimination of resting LV outflow tract gradients in nearly all patients, substantial improvement in heart failure symptoms, rapid onset and reversibility of effect, and the ability to use precise echo-guided titration without treatment interruptions,” said principal investigator Martin Maron, MD, director of the Hypertrophic Cardiomyopathy Center at Tufts University School of Medicine, in 

. “We look forward to investigating aficamten further in a large phase 3 clinical trial that we expect to start by year end.”

After showing promise in preclinical trials, the Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM (REDWOOD-HCM) trial was designed to further assess the potential effects of aficamten as a potential treatment for hypertrophic cardiomyopathy (HCM). A multicenter, randomized, placebo-controlled, double-blind, dose finding clinical trial, the trial randomized patients to receive 1 of 2 aficamten dosing regimens, which included echocardiography assessments to guide dose levels, or placebo therapy for 10 weeks.

For inclusion in the study, patients were required to be 18-85 years of age, have LV wall thickness of 15 mm or greater, symptomatic NYHA FC II-III obstructive hypertrophic cardiomyopathy, a baseline LVEF of 60% or greater, and on stable doses of background medical therapy. Outcomes of interest in the trail included resting and Valsalva LVOT, change in LVEF, NYHA class, NT-proBNP, and safety and tolerability.

Patients included in either of the aficamten cohorts were given 3 doses of the study drug, with cohort 1 receiving doses of 5, 10, and 15 mg and cohort 2 receiving doses of 10, 20, and 30 mg. At conclusion of the trial, 13 patients were included in the placebo group, 14 were included in aficamten cohort 1, and 14 were included in aficamten cohort 2. Investigators noted the 10-week treatment period of the study was followed immediately by a 2-week washout period.

Upon analysis, results from the trial suggested use of aficamten was associated with statistically significant reductions from baseline versus placebo in mean resting LVOT-G (

=.0004, Cohort 1 and Cohort 2, respectively) and in mean post-Valsalva LVOT-G (

<.0001, Cohort 1 and Cohort 2, respectively). Additionally, investigators pointed out 78.6% of patients in cohort 1 and 92.9% of patients in cohort 2 achieved the target goal of treatment, which was defined as a resting gradient less than 30 mmHg and a post-Valsalva gradient less than 50 mmHg at week 10. This was only achieved among 7.7% of patients in the placebo arm of the trial.

Additional observations highlighted included reductions in LVOT-G occurring within 2 weeks of initiating treatment, maximizing within 2-6 weeks of dose titration, and being sustained until the end of treatment at 10 weeks. Investigators noted reversibility of the pharmacodynamic effect of aficamten was observed after the 2-week washout period, when resting LVOT-G, post-Valsalva LVOT-G, NT-proBNP, and LVEF returned to baseline values. Further analysis indicated the observed reductions were dose-dependent.

Investigators also pointed out use of aficamaten was associated with significant reductions in NT-proBNP (

=.003) in both cohorts 1 and 2 compared to placebo. Additionally, an improvement of at least 1 NYHA class was observed among 31% of the placebo group compared to 43% (

 >.01) of patients in aficamten cohort 1 and 64% (

 =.08) of patients in aficamten cohort 2.

Redwood-HCM: A Randomized, Double-blind, Placebo-controlled, Dose-finding Trial Of The Cardiac Myosin Inhibitor, Aficamten, In Obstructive Hypertrophic Cardiomyopathy

Presented at HFSA 2021, results of REDWOOD-HCM provide insight into the effects of the oral selective cardiac myosin inhibitor aficamten in patients with obstructive hypertrophic cardiomyopathy. 

Aficamten Shows Potential for Hypertrophic Cardiomyopathy in REDWOOD-HCM

One of the most prominent discussions occurring at The Metabolic Institute of America’s (TMIOA) 2021 5th Heart in Diabetes sessions in New York, NY, centered around subpar uptake of newer medications, among endocrinologists, cardiologists, and other providers. 

Much of this discussion was related to advancing role of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of patients with diabetes and other cardiometabolic conditions, such as chronic kidney disease and heart failure.

This role, Matthew Budoff, MD, explained, is one that is being stalled by regulatory processes. In the second segment of an interview with our sister publication 

 at the meeting, Budoff, professor of medicine at David Geffen School of Medicine at UCLA, explained why the real-world uptake of newer cardiometabolic agents lags behind despite proven efficacy in clinical trials.

In this interview, Budoff explained, the US operates on a “general rule” that findings from 2 randomized trials may constitute a class I indication for a drug class. For example, he said, the DAPA-HF and EMPEROR trials supported the use of SGLT2 inhibitors for the reduced risk of heart failure in patients with and without diabetes. Budoff cited the CANVAS and EMPA-REG trials as supporting the drug class’ benefit in reducing composite cardiovascular death in patients with diabetes and atherosclerotic cardiovascular disease. Budoff went on to cite a trio of randomized clinical trials support GLP-1 receptor agonists for the reduction of composite coronary events, stroke, and all-cause death, he said.

For more on this topic, check out the video interview below:


Matthew Budoff, MD, discusses what he views as hurdles to achieving optimal prescription of newer agents in the treatment of cardiometabolic conditions, including diabetes, heart failure, dyslipidemia, and more. 

Matthew Budoff, MD: Need for Greater Uptake of Newer Medications

Results of PRESERVED-HF demonstrate use of dapagliflozin was associated with significant improvements in symptoms and physical limitations among patients with 

heart failure with preserved ejection fraction (HFpEF)

Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2021, results of PRESERVED-HF indicate use of dapagliflozin was associated with clinically meaningful improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and 6-minute walking distance, with these benefits evident after just 12 weeks.

“To our knowledge, PRESERVED-HF is the first trial to show compelling benefits of SGLT2 inhibitors on both patient-reported symptoms and physical limitations, as well as objectively measured physical function in individuals with HFpEF – outcomes of great importance to both patients and clinicians. It is especially meaningful for this disease condition, as HFpEF has been called the “black hole” of cardiology because until now we have not been able to find efficacious, disease modifying treatments,” said Mikhail Kosiborod, MD, cardiologist at Saint Luke’s Mid America Heart Institute and Vice President of Research at Saint Luke’s Health System, 

 “PRESERVED-HF shows that dapagliflozin can enable individuals with HFpEF to feel better and do more within just 12 weeks.”

Funded by AstraZeneca, PRESERVED-HF was designed as a multicenter, double-blind, randomized, placebo-controlled trial with the specific intent of assessing use of dapagliflozin 10 mg against matching placebo once daily for 12 weeks. Conducted across 26 sites in the US, the trial randomized a population of 324 patients, with 162 to each arm, and had a primary end point of change in KCCQ-OS at 12 weeks.

To be included in the trial, patients needed to have heart failure with NYHA class II-IV symptoms, a left ventricular ejection fraction of 45% or greater, NTproBNP of 225 pg/mL or greater, a requirement for diuretic therapy, and at least one of the following: a recent heart failure hospitalization or urgent visit requiring IV diuretic, elevated filling pressures by right or left heart catheterization, or structural heart disease by echocardiography. Notable exclusion criteria included hospitalization for heart failure within the previous 7 days, an eGFR less than 20 mL/min/m2, a history of type 1 diabetes or diabetic ketoacidosis, and planned or recent PCI, CABG, valve surgery, or CRT.

During his presentation, Kosiborod noted 57% of trial participants were women and approximately 30% were African American, which the aforementioned release highlighted as understudied groups in HFpEF. Kosiborod also pointed out about half of the patients included in the trial had diabetes or atrial fibrillation.

Upon analysis, results indicated use of dapagliflozin was associated with significant improvements in symptoms and physical limitations measured by the KCCQ-OS, with an effect size of 5.8 (95% CI, 2.3-9.2) points at 12 weeks (

=.001). In a secondary analysis, results demonstrated use of dapagliflozin was associated with a significant improvement in 6-minute walking distance compared to placebo therapy, with results indicating a difference in effect size of 20.1 (95% CI, 5.6-34.7) meters (

In a responder analysis, results suggested a greater proportion of patients on placebo therapy experienced deterioration r no change in KCCQ Clinical Summary Score at 12 weeks, while also demonstrating dapagliflozin use was associated with moderate-large or very large improvements (

=.01). In his presentation, Kosiborod highlighted no significant differences were observed for NTproBNP, BNP, HbA1c, or systolic blood pressure between the dapagliflozin and placebo arm of the study. Additionally, a modest weight reduction of 0.72 (95% CI, 0.01-1.42) kg was observed with dapagliflozin versus placebo therapy (

“Taken together with the results of previous studies, our findings further strengthen the notion that SGLT2 inhibitors represent a disease-modifying therapy, and thus an important new treatment option for HFpEF, which is a highly morbid condition. This is great news for patients and clinicians. As a cardiologist and researcher, I am excited about the potential impact of PRESERVED-HF data on the management of this patient population,” Kosiborod added.

This study, “Effects of Dapagliflozin on Symptoms, Function and Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction - Main Results from the PRESERVED-HF Trial,” was presented at HFSA 2021.

Presented at HFSA 2021, PRESERVED-HF provides evidence suggesting dapagliflozin use was associated with improvements in KCCQ symptom score and 6-minute walking distance in patients with heart failure with preserved ejection fraction. 

PRESERVED-HF: Dapagliflozin Reduces Symptom Burden, Physical Limitations in HFpEF

: An elderly lady with a history of DM who just switched from metformin to insulin is BIBA for sweats, light-headedness, nausea and SOB, all lasting about 1 hour. Her glucose was 68 by medics and symptoms resolved after juice and food that she was consuming as medics arrived. She denies any chest pain, abdominal pain, vomiting, or other complaints.

: Vital signs are normal as is her physical exam other than visible diaphoresis

Computer Read: Atrial pacemaker at 60 bpm, marked LAD, ST deviation and T-wave abnormalities consider inferior and anterolateral ischemia.

Our latest case report from Brady Pregerson, MD, features an elderly woman with a history of diabetes experiencing sweats, light-headedness, nausea, and SOB. Can you determine the correct diagnosis?


Cardiology Case Report: Hypoglycemia and Abnormal EKG


In a follow-up to earlier communications, the 

US Food and Drug Administration (FDA) announced

 the arthritis and ulcerative colitis medication tofacitinib (Xeljanz and Xeljanz, respectively) could lead to an increased risk of serious cardiovascular adverse events such as heart attack, stroke, cancer, blood clots, and death.

In a large, randomized clinical trial, tofacitinib was compared to tumor necrosis factor (TNF) blockers and results suggested an increased risk of blood clots and death was observed with the lower dose of Xeljanz, mirroring results reporting in an earlier DSC regarding higher doses of the medicine.

In their September 1 statement, the FDA announced that they are requiring new and updated warnings for baricitinib (Olumiant) and upadacitinib (Rinvoq), 2 other arthritis medicines in the same drug class as tofacitinib.

The 2 medicines have not yet been studied in similar large safety clinical trials like tofacitinib.

Despite this, they share the same mechanisms as tofacitinib, which lead to concerns from the FDA regarding similar risks.

Ruxolitinib (Jakafi) and fedratinib (Inrebic), 2 other JAK inhibitors used to treat blood disorders, are not indicated for the treatment of arthritis or other inflammatory conditions.

As such, they are not privy to the updates being required for the aforementioned drugs.

The FDA noted that further action will be taken if they become aware of any additional safety information or data regarding ruxolitinib or fedratinib that would warrant changes in prescribing information.

Announced in a statement on September 1, the FDA warning is an update to the FDA Drug Safety Communication issued on February 4, 2021 and the results of a review of a trial that found a serious increased risk of CV-related events with the drug. 

FDA Issues Warning Over Potential Cardiovascular Disease Risk with Tofacitinib

Month in Review: September 2021

Slideshows

September's cardiology month in review features FDA news relted to empagliflozin and tofacitinib, a study into the potential impact of sacubitril/valsartan's label expansion, and a study from HFSA 2021. 

Cardiology Month in Review: September 2021

As Practical Cardiology continues to grow and looks to engage more clinicians involved in cardiology, we have also added members to our editorial advisory board. Our eyes and ears in the field, our advisory board members help guide coverage to position us to provide high-quality editorial content for cardiologists and clinicians practicing or with an interest in cardiology. To allow our readers, viewers, and listeners an opportunity to become better acquainted with our advisory board members, we are launching the Meet the Board series. Periodically, we will be spotlighting content focused on our advisory board members and the reasons why they were chosen to help lead Practical Cardiology as we look to expand our audience and solidify our position as a leader in cardiovascular news.

In this edition of Meet the Board, you will be introduced to our advisory board chief Guy Mintz, MD, Director of Cardiovascular Health & Lipidology at North Shore University Hospital. The following is a transcript from a recent episode of 

 where Mintz provided insight into how the New York City-based lipid clinic he co-directs adapted to the different stages of the COVID-19 pandemic.

PC: Could you take me through a little bit of what is different about how the lipid clinic had to react versus the rest of the hospital?

 I think that's a great question. Now, one of the challenges during pandemic was connecting with patients because patients were avoiding the physicians and avoiding the hospitals, but at the lipid center we were able to adapt pretty easily because part of what we do is being involved in counseling, dietary recommendations, and reviewing blood tests. I think one of the most important aspects of the service that we provided was that patients were still able to connect with physicians, nurse practitioners, and dietitians. So, they had a medical person to actually speak to, and a lot of the questions we were answering at that time were pandemic-related as well. In terms of the lipid center, we were able to send home blood draws out into the community, so patients were getting their blood done. Many patients were working from home, or a lot of patients had tremendous stress and anxiety and were overeating or eating poorly or not taking their medications on regular basis.

So, I think one of the great services we provided was connecting with those patients, and kind of keeping them on an appropriate pathway. We really didn't miss a beat. For those patients that did need a blood test, the home blood draws were very safe and secure. We were able to get those results and contact the patient and, if they needed, contact a dietician. Now, dietary intervention is very amenable to telehealth because here you have the dietician actually seeing the patient's home and many of the patients would hold up a box of food and say, "Is a cereal good," or "I bought this pasta", and “Look at my refrigerator". So, I think it was a great opportunity for patients to really be comfortable and get better advice or more advice along the way.

Many of these patients had issues with blood pressure. They were able to take their blood pressure at home and we're able to counsel them with regard to blood pressure. So, I think, as a unit, we adapted very well.

I think the continued connection with patients with regard to just having a medical persona, for them to run things by was very important. Because, you know, the whole, you know, initiation of COVID-19 was scary, there was no information, there was a lot of misinformation. And I think we provided a comfort role. And we certainly did not miss a beat in managing these patients. So, lipid problems and giving them guidance for appropriate dietary intervention.

PC: How did the way you guys reacted to this pandemic change as we learned more about COVID-19?

 Well, as we moved from December of 2019 right up till the end of February, we were not aware that we were facing a COVID challenge and that was really business as usual. Now, being in New York, which was the epicenter of COVID-19, at that time, everybody was going out to celebrate the Chinese New Year at the end of February 2020 and celebrate St. Patrick's Day in March of 2020. Then the following week, on March 22-23rd, there was a new term—we have a pandemic. We have a hidden disease or hidden infectious agent that's going to be potentially devastating, and everything changed at that moment.

My office personally was open every day during the pandemic. The staff alternated one group in one week and off the second week, and vice versa. Doing it this way, if any of them "got sick", it would not devastate the office. So, in terms of what we did, we used N-95 masks with a surgical mask on top, goggles or eye coverings, and gowns. In certain situations, we used gloves, and only the patient was permitted in the room. So, we didn't have family members in the room unless the patient requires assistance or mental incompetence and needed a second person in the room. We were trying to really space everyone out and limit the exposure early on.

So, that was one piece. We were really trying to stay as protected as possible. The pace was slower because we were really cleaning our rooms and spraying and wiping and doing more than we had done before. So, we weren't turning the rooms over as quickly and that was okay because the volume was not the same. Our patients had to fill out questionnaires asking about potential exposures and such. Wearing masks for the patients was a challenge. Sometimes they were amendable and sometimes they did not quite understand it.

Fast forward to where we are today and we still mask in our office, we still wear gloves, we still take precautions, and we still adhere to the guidelines. Patients should be masked as well, and we are still trying to keep only the patient in the room and not significant others unless it's absolutely necessary. Unfortunately, some patients, you know, in 2021, and we can say August 2021, refused to wear masks in the waiting room, which goes against hospital policy. There's some issue there, but things have changed after the vaccinations became available, but there is still a lot of misinformation regarding the vaccinations. Our team was vaccinated early in December of 20 and had our second dose was very early in 2021.

We are still vigilant in our infectious protocols and wiping down the rooms and everything else because as you there is a Delta variant and there's another gamma variant, and it's still out there and still could affect people. So, our vigilance hasn't changed. Our approach hasn't changed. We try to educate the patients. In any given week, I may see five or six patients that still do not want to get vaccinated and, while that remains their choice, some of their rationale is not correct. We try to educate them every bit of the way. We're still doing some telehealth, but I think after patients became vaccinated, they became less reticent about coming into the physician's offices.

PC: Is there anything else about you want to add about the lipid center’s response to COVID-19?

 Just as another highlight, going back to the spring of 2020 where patients really did not seek medical attention, you had an increased number of myocardial infarctions where patients were not going to the hospital—they were ignoring symptoms of chest pain and shortness of breath.

So, I think we lost a lot of life at that point because patients just did not want to go near a hospital or couldn't connect with their physicians. I think if we ever had to face that type of challenge again, education and connecting with patients should be a paramount goal to what we do. Not only at the local level between your own patient population, but in terms of news and media. Letting patients know, if you have these symptoms, it is safe to go to the hospital. If you have any questions, call 911, and so on, so forth.

Every pathway that we took through the pandemic was a learning opportunity for us, as medical professionals, on how to best reach our patients, how patients would react in these types of situations, and, moving forward, how we could do it better. I think that begins and ends with communication, being available, and taking the time to explain things. Education means power. I like to say whether I'm educating my medical students, my fellows, of my residents, we all need to row in the same direction. If we can't row in the same direction the boat is spinning in a circle and we go nowhere. So, I think that's really important for what we do on a day-to-day basis.

As you highlighted before, I still think that 2021 and 2022 will be the year of the lipid. as well, as we've talked before the COVID-19 virus as a lipid capsule, and I believe the monoclonal antibodies are housed in a lipid case as well. So, we can't get away from lipids and cholesterol, no matter where you go. It's not just at Wendy's and McDonald's, but it's all over and patients need to understand that as well.

I think is important, not only for our clinicians but also for our patients, that very simply, patients that do get COVID-19 and have ongoing symptoms—the so-called group called the long-haulers. While many people are out there and say, "Oh, this is a benign thing. It's a three-day cold". Listen, we've seen 100 patients post-COVID with ongoing chest pain, ongoing shortness of breath, and I have many patients that have brain fog. So, even getting COVID and surviving and doing well, it doesn't leave patients necessarily as healthy as when they started. The post-COVID syndrome or long-haul syndrome is real, it affects many, and there are patients still from March of 2020 that still have the loss of sense of smell and loss of taste. So, I think that's also an important factor to highlight to the general public who need to know that it's not a one-and-done thing. It has certain consequences; the more cardiac risk factors someone has the greatest susceptibility they have to COVID-19 and COVID-19 could have deleterious effects. It's an all-encompassing virus and I think we need to be vigilant.

Editor's note: This transcript has been edited for length and clarity.

To allow our audience to become more acquainted with our advisory board members, Practical Cardiology will be hosting a special content series highlighting our board members, their practices, and why they were invited to help guide coverage moving forward.

Practical Cardiology's Meet the Board: Guy Mintz, MD

To address the growing obesity epidemic, the American Heart Association (AHA) has released new guidance outlining weight-loss strategies for the prevention and treatment of 

With data suggesting more than 100 million in the US have hypertension, the scientific statement outlines the need for effective, long-term solutions to weight loss to maintain reductions in hypertension and also calls for clinicians to consider other avenues outside of lifestyle modification for weight loss, such as medications and metabolic surgery.

“Weight loss achieved through dietary changes and increased physical activity are the cornerstones of treatment for high blood pressure that’s related to being overweight. However, these lifestyle behaviors are often not sustained over the long term. Subsequently, reductions in blood pressure aren’t maintained over time,” said Chair of the statement writing group Michael E. Hall, MD, MS, FAHA, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson, Mississippi, in 

. “The new scientific statement suggests medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity.”

The AHA’s scientific statement, which is 13 pages in length and contains nearly 100 references, opens by providing clinicians with an overview of epidemiology and pathophysiology of obesity hypertension before diving into avenues for reducing body weight, including lifestyle modification, pharmacotherapy, and bariatric procedures. Underlining the AHA’s stance from their June 2021 statement, the present statement, which was prepared on behalf of the AHA’s Council on Hypertension, the Council on Arteriosclerosis, Thrombosis, and Vascular Biology, the Council on Lifestyle and Cardiometabolic Health, and the Stroke Council, outlines the importance of dietary interventions and physical activity as first-line treatment for weight loss and hypertension control, but investigators were quick to point out these changes can be difficult to maintain long-term and can lead to recurrent increases in hypertension.

“There’s no doubt that eating healthy foods has beneficial effects on both weight and blood pressure,” Hall explained. “Numerous weight-loss diets are often successful in the short term; however, eating healthy foods consistently and long term, and maintaining weight loss are challenging.”

The next portion of the statement called for an increase in consideration of pharmacologic therapies for obesity hypertension, if lifestyle modifications have proven unsuccessful in achieving weight reduction and blood pressure control. In addition to FDA approved therapies for long-term weight loss, authors highlight the latest revelations related to the potential for reductions in body weight and blood pressure seen with GLP-1 receptor agonists. Specifically, liraglutide and once-weekly semaglutide 2.4 mg, which was not yet approved at the time of writing, were highlighted by statement authors.

“We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke. However, we may be able to prevent these complications. When combined with lifestyle changes, anti-obesity medicines and surgical procedures can be effective long-term solutions for weight loss and blood pressure control in select individuals who are overweight or have obesity,” Hall added.

The last treatment approach discussed within the statement highlighted surgery for weight loss. Although considered a newer approach to mitigating the effects of obesity, authors point out the popularity and safety of these procedures have grown in recent years. According to the statement, more than 215,000 metabolic procedures were performed in 2016, with the most popular being sleeve gastrectomy followed by Roux-en-Y gastric bypass. With these types of procedures typically reserved for candidates with a BMI at or equal to 35 kg/m2, investigators point out observational data suggests bariatric procedures could contribute tor solution of hypertension in 63% of procedures. Additionally, authors highlight the contributions of the GATEWAY trial, as it is the only controlled trial involved metabolic surgery with blood pressure as a primary end point, to our current understanding of the effects of metabolic surgery. In that trial, patients were 6 times more likely to experience resolution of hypertension with metabolic surgery than they were with standard medical therapy.

“Metabolic surgery techniques are continuing to evolve, and they are getting less invasive and less risky,” Hall said. “For select individuals, medications or metabolic surgery or both may be considered in addition to healthy diet and increased physical activity.”

Before the conclusion of their statement, authors highlighted what they perceive as areas in need of further research related to obesity hypertension. Specific research recommendations included the need for more randomized trials in the space, research into the mechanisms of obesity-related diseases, and the need for a greater understanding of the long-term safety and efficacy of various treatment and prevention strategies.

“There are still many unanswered questions and many opportunities for research that can help people live healthier, longer,” Hall added.

Weight-Loss Strategies for Prevention and Treatment of Hypertension,

The American Heart Association has released a scientific statement outlining the current knowledge base surrounding potential prevention and treatment strategies for the management of obesity hypertension. 

AHA Releases Guidance for Weight Loss Strategies to Combat Obesity Hypertension

As a cardiovascular researcher with interests across most areas of cardiology therapeutics and diagnostics, I found HFSA 2021 a treasure trove of heart failure (HF)-related topics. As a PA in a general cardiology/lipidology-oriented practice with mostly outpatient and only very occasional opportunities for inpatient management, HFSA was almost overwhelming because of that depth and breadth of heart failure learning offerings.

In full transparency, HFSA is not generally a conference on the radar of this general cardiology/lipidology PA. I usually rely on my excellent Intermountain Heart Institute Heart Failure/Transplant colleagues to update me after they attend this conference. Through my recent engagements as the current President of the Association of PAs in Cardiology (APAC) to improve PA involvement and advocacy in HFSA, I was invited to co-moderate a Saturday session, “Deep Learning for HF Medicine: A Practical Primer” alongside Maria Rosa Costanzo, MD, and ultimately presented a talk as well in the same session. Nearer to the conference date, I was asked to also join in as a PA discussant on the final Monday session of the conference titled “Clinical Conundrums – Multidisciplinary Case Discussion”.

I thoroughly enjoy attending scientific conferences and find that the researcher in me gravitates strongly towards developing my attendance itinerary around Late-Breaking Clinical Trial content. Personally, my engagement/attention level increases as an invited faculty member and/or as a presenter of submitted research (e.g. oral or poster abstract).

In all honesty, I identify as an introvert in most settings and often experience anxiety in unfamiliar settings, such as being a first-time conference goer at a conference in an area of cardiology that is not a focus of my clinical or research practice. To combat this, I often make connections in a “safe space” via social media or reach out to those colleagues I know who are attending (e.g., Kevin Shah, MD, and Sarah Schroeder, ACNP) and meet when possible. Part of the driving factor for me to advocate for PAs within HFSA as President of APAC is to develop infrastructure for PAs to welcome one another, collaborate, and network within HFSA and especially face-to-face at conferences (masked and vaccinated of course!). Wearing my President of APAC hat did lend me the courage to walk up to one of two PAs that I encountered at HFSA. The other PA was introduced to me via my friend and HF colleague, Sarah Schroeder, ACNP. I hope to continue to build on this collaboration between APAC and HFSA and outreach to PAs in HF.

With all the above as background to provide context of my first HFSA experience, I arrived with a strength of purpose knowing that I needed to be prepared to co-moderate, provide a specific talk on Deep Learning, and be ready to provide PA specific input to a multidisciplinary discussion on clinical cases. I then planned my itinerary to try and include Late-Breaking Clinical Trials. Finally, as an attendee without the framework of seeing patients that are majority HF-related, I split the rest of my day in visiting and engaging with poster presenters and attending sponsored evening presentations.

The Heart Failure Society of American (HFSA) 2021 Scientific Sessions was planned as a hybrid conference, blending the traditional in-person meeting with a virtual attendance option. I appreciated the lengths to which the HFSA conference planners took to help mitigate covid infections as in-person attendees were asked to demonstrate full vaccination status and to remain masked while attending indoor events.

While hybrid sessions can and sometimes did feel “clunky” both as moderator and attendee, I congratulate the HFSA committee for being intentional about this still “fairly” new conference modality. In my view, being intentional about recording live in-person sessions that have synchronous virtual attendees provides one watching these sessions later with a “real experience”. Many attendees, including myself may not always (or ever) feel comfortable standing at a microphone in a crowd to ask a question. Providing that capability via Slido software did allow me to ask my question “virtually” while sitting in-person. Thus, reducing my crowd-anxiety yet allowed me to ask a question I felt was important.

My final words of advice for the first-time attendee. It is okay to have conference anxiety. Plan ahead by reviewing the conference planner and identify subjects that you are passionate about, consider stopping in at poster presentations to see new and evolving science, one can never go wrong with late-breakers, consider submitting science or proposals to speak on a topic, and lastly, connect with others ahead of conference and plan to meet up or go to sessions with your colleagues.

Viet Le, PA-C, details his experience at the Heart Failure Society of America annual meeting from the perspective of a physician assistant.  

HFSA 2021: The Physician Assistant's Experience, With Viet Le, PA-C

New research from a trial conducted by investigators at the Cleveland Clinic is underscoring the impact of dietary choices and interventions in reducing cardiovascular risk factors among children with overweight or obesity.

An assessment of 3 specific eating patterns in children aged 9-18 years old with a BMI in the 95th percentile or greater, results of the study provide evidence suggesting adherence to either of the 3 diets examined in the trial could result in significant improvements in cardiovascular risk factors among this patient population.

“This study helps show the importance of starting healthy eating patterns as young as possible. We know that cardiovascular disease begins in childhood, and children's eating patterns are easier to mold than adolescents and adults,” said lead investigator Michael Macknin, MD, professor emeritus of pediatrics of Cleveland Clinic Lerner College of Medicine, in 

With an interest in further exploration of the impact of dietary choices on cardiovascular risk and risk factors among pediatric considered overweight or obese, Macknin and colleagues at the Cleveland Clinic designed the current study as a prospective randomized trial comparing the effects of the American Heart Association Diet, Mediterranean Diet, and a plant-based diet for 52 weeks from patients within the Cleveland Clinic’s Pediatric Obesity Registry. For inclusion in the trial, patients needed be 9-18 years of age, have a BMI for age and sex in the 95th percentile, and a total cholesterol greater than 169 mg/dL.

Ultimately, 96 child-caregiver dyads were identified for inclusion in the trial. Patients included in the study were asked to attend educational sessions to learn more about their assigned diets and receive support. Anthropometric measurements, including weight, BMI, blood pressure, and waist circumference, were recorded at weeks 0, 4, and 52. Investigators used fasting blood tests to assess biomarkers of risk including total cholesterol, LDL-C, HDL-C, and hsCRP.

Each of the 3 study arms contained 32 children and 32 parents or guardians. Of these 96 dyads, 83% attended the first study visit, 70% attended the 4-week visit, and 33% completed the 52-week visit. Investigators pointed out the small sample sizes resulted in inadequate power to detect significant differences in study results associated with participation in education sessions and study visits.

Upon analysis, results suggested significant improvements were observed in all groups at 4 weeks when examining weight, systolic and diastolic blood pressure, and myeloperoxidase. Additionally, similar statistically significant results were observed for total cholesterol and LDL-C. When assessing reasons for opting not to enroll in the study, time was identified as the only significant deterrent (

“Because the process of heart disease begins in childhood, prevention should begin there as well,” said W.H. Wilson Tang, MD, study author and research director in the section of heart failure and cardiac transplantation medicine in the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. “A large majority of heart disease is due to modifiable or controllable risk factors, so it’s important for children to understand that they are in large part responsible for their health.”

Three Healthy Eating Patterns and Cardiovascular Disease Risk Markers in 9 to 18 Year Olds With Body Mass Index >95%: A Randomized Trial

A trial comparing 3 eating patterns suggests a healthy dietary approach could lower cardiovascular risk factors among pediatric patients considered to be overweight or obese. 

Cardiology Month in Review: September 2021

Practical Cardiology's Meet the Board: Guy Mintz, MD

AHA Releases Guidance for Weight Loss Strategies to Combat Obesity Hypertension

HFSA 2021: The Physician Assistant's Experience, With Viet Le, PA-C

Healthy Eating Patterns Can Reduce Cardiovascular Risk in Children Considered Overweight or Obese