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New data from an analysis of the landmark DELIVER trial is providing clinicians with insight into the effects of dapagliflozin (Farxiga) on 

 and KCCQ scores among people with heart failure with preserved ejection fraction (HFpEF) across the spectrum of body weight.

A prespecified analysis of the phase 3 trial, which was 

, investigators detail the effects of dapagliflozin across 5 different body weight categories, with results indicating dapagliflozin reduced the risk of the trial’s primary composite out to a similar extent across World Health Organizations BMI categories.

“Obesity is common in patients with HFpEF and is associated with higher rates of heart failure hospitalization and worse health status. Treatment with dapagliflozin improves cardiovascular outcomes across the spectrum of BMI, leads to greater symptom improvement in patients with obesity, compared with those without, and has the additional benefit of causing modest weight loss,” wrote investigators in their conclusion.

As the obesity epidemic continues to grow in the US and abroad, knowledge related to the effects of guideline-directed medical therapies for various disease states serves to have a substantial impact on patient care. With this in mind, the current study was designed as a prespecified analysis of the phase 3 DELIVER trial, which randomized more than 6200 patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF to dapagliflozin or placebo therapy with a primary endpoint defined as a composite of worsening heart failure and cardiovascular death.

In the original trial, a primary outcome event was identified among 16.4% (n=512) of the dapagliflozin group and among 19.5% (n=610) of the placebo group (HR, 0.82 [95% CI, 0.73 to 0.92]; 

 <.001) during a median of 2.3 (IQR, 1.7 to 2.8) years of follow-up. Further analysis indicated use of dapagliflozin was associated with a reduction in rate of hospitalization for heart failure or urgent visit for heart failure (HR, 0.79 [95% CI, 0.69 to 0.91]) and cardiovascular death (HR, 0.88 [95% CI, 0.74 to 1.05]) compared with placebo.

Of the 6263 who underwent randomization in the DELIVER trial, 6257 had a recorded BMI measurement at baseline. Among these, 21.5% were considered normal weight, 33.1% were considered overweight, 25.2% had Class I obesity, 12.8% had Class II obesity, and 6.6% had Class III obesity, according to WHO criteria. Compared to their counterparts with normal BMI, those with obesity were younger, more often female, more likely to be White. Investigators also noted patients with obesity also had higher systolic and diastolic blood pressure, a higher HbA1c, and were more likely to have a diagnosis of type 2 diabetes than patients with a normal weight.

Upon analysis, results indicated use of dapagliflozin was associated with similar reduction in risk of the trial’s primary outcome across BMI categories, with HRs of 0.89 (95% CI, 0.69 to 1.15) for normal weight, 0.87 (95% CI, 0.70 to 1.08) for overweight, 0.74 (95% CI, 0.58 to 0.93) for Class I obesity, 0.78 (95% CI, 0.57 to 1.08) for Class II obesity, and 0.72 (95% CI, 0.47 to 1.08) for Class III obesity (

for interaction=.82). Further analysis suggested the effects of dapagliflozin on out outcomes, including cardiovascular death, worsening heart failure, total heart failure events, and all-cause mortality, were consistent across BMI categories (

Among the 6257 included in this prespecified analysis, 5792 had KCCQ-TSS scores recorded at baseline and 4485 had a recorded measurement at 8 months. When assessing change in KCCQ-TSS scores, results indicated the degree of improvement associated with Dapagliflozin use was greater in those with higher BMIs, with a placebo-corrected change of 0.9 (−1.1, 2.8), 2.5 (0.8, 4.1), 1.9 (−0.1, 3.8), 2.7 (−0.5, 5.8), and 8.6 (4.0, 13.2) points, among those with normal weight, overweight, Class I obesity, Class II obesity, and Class III obesity, respectively (

 for interaction=.03). In analyses assessing change in body weight, results indicated t , with a placebo-corrected weight loss of –0.88 (−1.28, –0.47) kg among those considered normal weight, –0.65 (−1.04, –0.26) kg among those considered overweight, –1.42 (−1.89, –0.94) kg among those with Class I obesity, –1.17 (−1.94, –0.40) kg among those with Class II obesity, and –2.5 (−4.4, –0.64) kg among those with Class III obesity (

“The key finding of this study was that dapagliflozin was equally efficacious in reducing the primary composite outcome of worsening HF or cardiovascular death across the spectrum of BMI in DELIVER, including among participants who were obese. Treatment with dapagliflozin also led to an improvement in symptoms measured with the KCCQ-TSS and which was greater in patients with a higher BMI,” investigators added.

Dapagliflozin for heart failure according to body mass index: the DELIVER trial

Articles

A prespecified analysis of the DELIVER trial details the effects of dapagliflozin across World Health Organization BMI categories among people with heart failure with preserved ejection fraction included in the phase 3 trial.

Dapagliflozin Provides Consistent Benefit Across Spectrum of Body Weight in HFpEF

An analysis of data from more than 100,000 individuals living in Europe is providing insight into the risk of 

 associated with consumption of artificial sweeteners.

A web-based prospective cohort study conducted in France, results of the study indicate consumption of artificial sweeteners was associated with a 9% increase in risk of cardiovascular disease, with further analysis breaking down the risk observed by individual sweeteners, including aspartame, acesulfame potassium, and sucralose.

“In the NutriNet-Santé cohort, total artificial sweetener intake was associated with increased risk of overall CVD and cerebrovascular disease. Aspartame intake was associated with increased risk of cerebrovascular events, and acesulfame potassium and sucralose were associated with increased coronary heart disease risk. Our results suggest no benefit from substituting artificial sweeteners for added sugar on CVD outcomes,” wrote investigators.

Since the late 1990s and early 2000s, artificial sweeteners have increased in popularity as ultra-processed food and artificially sweetened beverages have become more common staples in diets across the globe. Conducted by a team from the University of Paris and the French Network for Nutrition and Cancer Research, investigators designed their population-based prospective cohort study to evaluate association between artificial sweeteners and risk of cardiovascular disease.

Launched in 2009, the NutriNet-Santé e-cohort was created with the intent of assessing relationships between nutrition and health. Hailed as the world’s largest nutrition study, the web-based cohort contains data related to more than 170,000 adults aged 15 years or older who completed online questionnaires about diet, health, anthropometric data, lifestyle and sociodemographic data, and physical activity. Overall, 103,388 participants were identified for inclusion in the current study. These patients had a mean age of 42.2±14.4 years, 79.8% were female, and had a total of 904,206 person-years of follow-up data.

Of those included, 37.1% reported consumption of artificial sweeteners, with an average intake of 15.76 mg per day among all participants and 42.46 mg per day among consumers. Investigators pointed out associations between sweeteners and cardiovascular risk were estimated using multivariable-adjusted Cox hazard models.

Upon analysis, results indicated total artificial sweetener intake was linked to an increased risk of cardiovascular disease (HR, 1.09 [95%CI, 1.01-1.18]; 

=.03). Further analysis of individual sweeteners demonstrated consumption of aspartame was associated with an increased risk of cerebrovascular events (HR, 1.17 [95% CI, 1.03-1.33]; 

=.02) while consumption of acesulfame potassium (HR, 1.40 [95% CI, 1.06-1.84]; 

=.02) and sucralose (HR, 1.31 [95% CI, 1.00-1.71]; 

=.05) were associated with increased risk of coronary heart disease.

“These findings suggest that higher artificial sweetener consumption might be associated with increased risk of CVDs. Further well-designed, large-scale prospective studies need to confirm these results and experimental studies should be conducted to clarify biological pathways. In the meantime, this study provides key insights into the context of artificial sweetener re-evaluation by the EFSA, WHO, and other health agencies worldwide,” investigators added. “Our results indicate that these food additives, consumed daily by millions of people and present in thousands of foods and beverages, should not be considered a healthy and safe alternative to sugar, in line with the current position of several health agencies.”

Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort

An analysis of the NutriNet-Santé cohort provides insight into the apparent increase in cardiovascular disease risk associated with consumption of artificial sweeteners. 

Artificial Sweetener Consumption Linked to Increased Cardiovascular Disease Risk

New research from the University of California, San Francisco is highlighting the potential impact of optimal dietary adherence to a DASH diet on cardiovascular disease risk among young and middle-aged adults with

Presented at the American Heart Association’s Hypertension Scientific Sessions, results of the simulation study suggest adherence to the Dietary Approaches to Stop Hypertension (DASH) diet along with other behavior modifications could prevent up to 26,000 cardiovascular disease events and 2900 deaths while also saving $1.6 billion in associated healthcare costs over the course of a decade.

“Nearly nine million young and middle-aged adults with untreated stage 1 hypertension represent a significant, impending burden for health care systems,” said Kendra D. Sims, PhD, MPH, a postdoctoral fellow at the University of California, San Francisco and co-lead researcher of the study, 

. “Our results provide strong evidence that large-scale, healthy behavior modifications may prevent future heart disease, related complications and excess health care costs.”

The present study is one of many recent studies born out of the lowering of the diagnostic threshold for hypertension within the 2017 ACC/AHA guidelines. As part of these guidelines, clinicians were encouraged to counsel patients on the impact of behavior modification. Together with colleagues from UCSF, the current study was designed with an interest in assessing the potential population-level benefits of behavioral modification on cardiovascular disease risk among patients now meeting the diagnostic criteria for stage 1 hypertension. With this in mind, investigators conducted a study using the Cardiovascular Disease (CVD) Policy Model to simulate cardiovascular disease events, mortality, and healthcare costs among the aforementioned population from 2018-2027.

Using data from the 2015-2018 cycles of the National Health and Nutrition Examination Survey (NHANES), investigators identified a population of adults that was representative of 8.6 million adults aged 35-64 years with untreated stage 1 hypertension within the US. Who were defined as being lower-risk individuals based on not having diabetes, chronic kidney disease, history of cardiovascular disease, or a 10-year CVD risk exceeding 10%. Additional forms of behavior modification of interest for the present study included alcohol consumption, smoking cessation, and physical activity. For the purpose of analysis, the effects of dietary modification, sustain weight loss, physical activity, smoking cessation, and alcohol moderation were derived from published meta-analyses and trial data. Investigators pointed out that 50.6% of the estimated 8.7 million US adults included in the study were women and 61% had regular healthcare access.

Upon analysis, investigators found controlling systolic blood pressure to less than 130 mmHg in the entire target population could prevent 27,000 cardiovascular ease events, avoid 2800 deaths, and save an associated $16 million in healthcare costs during the study period. Further analysis indicated the greatest degree of benefit would be derived from the adoption of the DASH Diet, which investigators purport could prevent an estimated 16,000 cardiovascular disease events among men and 11,000 such events among women.

“Members of many disadvantaged communities face barriers to healthy food and regular health care access,” Sims added. “This means they will not be able to benefit from a counseling from a doctor. Future research should investigate the big picture: social conditions granting people the time and resources to make healthy lifestyle choices. Only with this information can we develop policies for the prevention of heart disease, especially for vulnerable adults.”

Projected Impact Of Non-pharmacologic Management Of Stage 1 Hypertension Among Lower-risk U.S. Adults

A new study from the AHA's Hypertension Scientific Sessions provides an overview of the potential population-level benefit of behavior modification, including adherence to a DASH diet, on CVD events and mortality among patients with stage 1 hypertension.

DASH Diet Could Prevent 25,000+ Cardiovascular Events in those with Stage 1 Hypertension

The US Food and Drug Administration (FDA) has approved an expanded indication for the current-generation WATCHMAN FLX Left Atrial Appendage Close (LAAC) Device to include a 45-day 

 option as an alternative to the postprocedural oral anticoagulation (OAC) plus aspirin regimen for patients with 

Announced in a September 6 release, the expanded indication is based on recent clinical evidence submitted to the FDA in support of the safety and efficacy of DAPT as a postprocedural antithrombotic regimen in patients with NVAF seeking an alternative to OAC, including analyses of 8300 patients from the American College of Cardiology Foundation's National Cardiovascular Data Registry (NCCDR) Left Atrial Appendage Occlusion (LAAO) Registry.

"This revised labeling provides physicians more flexibility to exercise their clinical judgment based on individual patient characteristics to determine the most appropriate postprocedural antithrombotic medication regimen," said Ian Meredith, MBBS, PhD, global chief medical officer at Boston Scientific, in the aforementioned release. "This significant step forward is supported by the robust safety and efficacy profile demonstrated by both the legacy WATCHMAN and current-generation WATCHMAN FLX technologies."

initial approval of the WATCHMAN FLX LAAC Device coming in July 2020

, the latest label expansion allows the choice of either OAC or a DAPT postprocedural drug regimen, which has been part of the labeling in Europe for WATCHMAN technology since 2017, according to Boston Scientific. Hailed by the company as being ultimately on the “most studied and implanted LAAC device in the world”, the initial approval of the WATCHMAN FLX device was based on results of the PINNACLE FLX trial.

In their release, Boston Scientific highlighted recent data supporting use of the WATCHMAN FLX device, including analysis of 17,000 from NCDR-LAAO Registry suggests no significant difference in rates of major adverse events at 45 days postimplant, whether patients were discharged from the hospital on DAPT, a direct OAC and aspirin, or warfarin and aspirin. The release also called attention to data from SURPASS analysis from NCDR-LAAO Registry demonstrating low rates of adverse events and peri-device leak through 45 days postimplant, and, in the investigator-led SEAL-FLX study, which Boston Scientific purports is the first study exclusively comparing WATCHMAN FLX device against the Amplatzer Amulet device.

FDA summary of recently sponsored devices

, the administration points out WATCHMAN devices should not be used in patients with a blood clot in their heart, who have had surgical repair of the atrial septum or have a device placed in the atrial septum, who have an LAA that is too large or too small to fit the WATCHMAN or WATCHMAN FLX device, cannot have blood-thinning medicines, or who have sensitivity to Nitinol or any other material that is part of the device.

Announced by Boston Scientific on September 6, the label for the WATCHMAN FLX LAAC device now includes a 45-day DAPT option as an alternative to the 45-day postprocedural OAC plus aspirin regimen for patients with nonvalvular atrial fibrillation.

FDA Expands WATCHMAN FLX Approval to Include DAPT Option

A patient in their mid-50s presents to the hospital with right leg swelling that started 4 days ago. He reports sudden leg swelling associated with constant 4/10 leg pain. He says his leg feels hard and is making him limp. He denies trauma or excessive exercise, chest pain, SOB, or other complaints.

Vital signs are normal except for a pulse in the 120s. The physical exam is notable for tachycardia and a swollen firm leg.

: sinus tach at 116, nonspecific ST abnormality

Our latest cardiology case report from Brady Pregerson, MD, features a man in his mid-50s presenting to the hospital with leg swelling that started 4 days ago but denies chest pain, SOB or other complaints. Check out the ECG and determine the correct diagnosis. 

Cardiology Case Report: Right Leg Pain, Swelling

As the COVID-19 pandemic continues, now in its third year, we have learned and continue to learn much about the cardiovascular complications that arise as a result of the novel coronavirus infection.

At this point in the pandemic’s trajectory both macrovascular and microvascular sequelae of the virus have been identified including thromboembolism, heart muscle injury, heart failure, and arrhythmias.

 Historically it has been difficult to study pregnancy related complications due to the difficulty in enrolling pregnant participants.

In keeping with their mission to stay on the cutting edge of cardiovascular care, the American College of Cardiology (ACC) Cardiovascular Disease in Women Committee reviewed all the available data in an effort to determine the specific cardiovascular risks for pregnant women who are infected with the COVID-19 virus.

Building on evidence from the US Centers for Disease Control and Prevention (CDC) who found that pregnant women are at increased risk of adverse outcomes with COVID-19, the ACC committee found that infected pregnant women are at higher risk for pre-term birth and still birth when compared to pregnant women not infected with the virus.

 Further it was found that one third of infants born to women with COVID-19 required neonatal intensive care.

It is well known that those with preexisting conditions are at higher risk for severe COVID-19 related disease, hospitalization, and death.1 Results of this current investigation indicate that pregnancy itself may be considered a preexisting condition putting women at much higher risk if infected by COVID-19. More specifically the ACC committee found that pregnant women infected with COVID-19 are at greater risk for intensive care unit admission, mechanical ventilation, and extracorporeal membrane oxygenation support when compared to nonpregnant women of reproductive age.

With regards to cardiovascular complications in pregnant women with COVID-19, reports were found of myocardial damage, arrythmias, and heart failure, but more data will be required to determine if the prevalence of these complications differs between pregnant and non-pregnant women. Similarly, it remains unclear if the rates of preeclampsia, peripartum cardiomyopathy, and spontaneous coronary dissections can be distinguished from other COVID-19 CV complications.

In addition to pregnancy specific complications, pregnant women with more traditional comorbidities associated with poor outcomes after COVID-19 infection are at even higher risk for complications including severe disease and death.

 Racial disparities were also found. Non-Hispanic Black women represented over one quarter of pregnancy associated deaths in one U.S. study while pregnant Hispanic women saw a 2.4-fold increase in death, Asian and Native Hawaiian/Pacific Islanders had the highest intensive care unit admissions.

Although it is clear that pregnancy is responsible for a unique cardiovascular risk profile during COVID-19 infection it is unclear why. The authors propose that a key reason could be that pregnant women generally have lower vaccination rates compared to non-pregnant women.

 In fact, in one study cited by the committee, three quarters of pregnant women requiring hospitalization with COVID-19, the overwhelming majority of those requiring intensive care admission, and all of the fetal deaths occurred in unvaccinated women.

With the COVID-19 pandemic showing no sign of retreat pregnant women need to know the facts.

“Pregnant people need to know that they are at increased risk of a severe COVID-19 infection, including ICU admissions, cardiac complications, need for critical care and death for the patient or fetus. Unfortunately, pregnant women have lagged behind other groups getting vaccinated,” wrote lead author Joan Briller, MD, of the University of Illionois.

The authors of this report want women to know that all available data support vaccination for COVID-19 in pregnancy with both an excellent safety profile and protection for the infant once born.

 More research is needed to determine how to differentiate between COVID-19 complications and those attributable to pregnancy and COVID. The committee suggests that, in the meantime, “Pregnancy Heart Teams” should be created and responsive to presumed pregnant COVID-19 admissions.

These teams should be multidisciplinary and include high risk obstetricians, obstetric anesthesia, cardiologists, and experts in adult and neonatal critical care.

 Armed with the knowledge that COVID-19 in pregnant women has its own unique considerations we can provide care tailored to this patient population in the hopes of saving the lives of mothers and babies through and hopefully after the pandemic.

1. Briller JE, Aggarwal NR, Davis MB, Hameed AB, Malhamé I, Mahmoud Z, McDonald EG, Moraes de Oliveira G, Quesada O, Scott NS, Sharma J; American College of Cardiology Cardiovascular Disease in Women Committee. Cardiovascular Complications of Pregnancy-Associated COVID-19 Infections. JACC Adv. 2022 Aug 10:100057. doi: 10.1016/j.jacadv.2022.100057. Epub ahead of print. PMID: 35967591; PMCID: PMC9364954.

In his most recent column, Dr. Gregory Weiss provides an overview of a recent American College of Cardiology report detailing apparent increases in cardiovascular risk observed among pregnant women infected with COVID-19.

COVID-19-Related Cardiovascular Complications in Pregnancy, with Gregory Weiss, MD

European Society of Cardiology (ESC) Congress 2022

 may be over, our editorial team is recapping the most popular new trial data from the ESC’s first in-person conference since 2019. The top 5 trials, which were chosen based on total views per article, includes DELIVER, TIME, AXIOMATIC-SSP, FIDELITY, and DANCAVAS.

1. Dapagliflozin Proves HFpEF Benefit in DELIVER Trial

Less than 3 months after AstraZeneca announced the trial had met its primary endpoint back in May, full results of DELIVER were presented at ESC Congress 22. Results of the DELIVER trial indicate use of dapagliflozin (Farxiga) was associated with an 18% reduction in the primary outcome, with a 21% reduction in risk observed for worsening heart failure and a 12% reduction in risk observed for cardiovascular death compared with placebo therapy. Results of the study build on the evidence from previous dapagliflozin trials contribute to the idea that the benefits seen in HFpEF could be a class effect for SGLT2 inhibitors.

2. TIME Study: No Added Benefit from Nighttime Dosing of Blood Pressure Medications

Although the Hygia study produced evidence suggesting nocturnal dosing could improve outcomes, results of the randomized trial, which included 21,104 patients followed for more than 5 years, demonstrate evening dosing did not result in a significant difference in cardiovascular outcomes among patients with hypertension included in the trial compared to standard morning dosing.

“People with high blood pressure should take their regular antihypertensive medications at a time of day that is convenient for them and minimizes any undesirable effects,” said lead investigator Professor Thomas MacDonald.

3. Milvexian Shows Promise for Preventing Stroke in Phase 2 Dose-Finding Trial

In what the European Society of Cardiology press release referred to as the largest dose-finding trial of an anticoagulant in a stroke population, the phase 2 AXIOMATIC-SSP trial provides evidence suggesting use of milvexian in patients with a prior ischemic stroke or high-risk transient ischemic attack could reduce risk of stroke without an increase in clinically significant bleeding events.

4. Finerenone Reduces All-Cause Mortality, Sudden Cardiac Death in Type 2 Diabetes

With pooled data from the FIDELIO-DKD and FIGARO-DKD trials, an analysis of the FIDELITY program from ESC Congress 2022 details an 11% reduction in risk of all-cause mortality and a 25% reduction in risk of sudden cardiac death among patients with type 2 diabetes and chronic kidney disease.

5. DANCAVAS: Universal CVD Screenings Do Not Reduce Risk of Death in Men

Results of a population-based trial assessing the impact of universal subclinical CVD screenings among men aged 65-74 years living in 15 Danish municipalities found increased screenings did not significantly reduce the risk of all-cause mortality in men aged 65-74 years over the next 5 years.

Although the European Society of Cardiology (ESC) Congress 2022 may be over, our editorial team is recapping the most popular new trial data from the ESC’s first in-person conference since 2019. The top 5 trials, which were chosen based on total views per article, includes DELIVER, TIME, AXIOMATIC-SSP, FIDELITY, and DANCAVAS.

Top New Trial Data at ESC Congress 2022

Results of a single-group, premarket clinical study suggest a major advance in implantable cardioverter-defibrillators (ICD) could be on the horizon.

Sponsored by Medtronic, results of the study, which were presented at the 

, provide insight into the use of an external ICD system, including the proportion of event-free patients at 6 months and lack of intraprocedural complications observed with the system.

"This study is encouraging. By placing the lead in this new position behind the sternum, the uncommon but serious risks associated with transvenous ICDs, such as lung collapse, damage to heart valves and heart perforation, can be avoided. Limitations of the subcutaneous ICD are also overcome. Since the lead is behind the sternum and close to the heart, pacing can be delivered, and defibrillation requires less energy with a longer battery life than with the subcutaneous ICD," said lead investigator Paul Friedman, MD, a cardiac electrophysiologist, 

After a 3-month pilot study examining use of an extravascular ICD demonstrated safety and efficacy of the device, the current study was conducted with the intent of examining the extravascular ICD . Named the global Extravascular ICD Pivotal Study, the current study was designed as a prospective, global, multicenter, single-group, nonrandomized, premarket approval study with the aim of enrolling up to 400 patients with a class I or II indication for an ICD for primary tr secondary prevention at up to 60 sites.

The primary efficacy outcome of interest for the trial was successful defibrillation at implantation, which was defined as the termination of an induced sustain shockable ventricular arrhythmia either with one 20-j shock or with 30 J on 2 consecutive episodes. The primary safety outcome of interest was freedom from major system- or procedure-related complications at 6 months. Investigators determined their efficacy objective would be met if the lower boundary of the one-sided 97.5% CI for percentage of patients with successful defibrillation was greater than 88%. For the safety objective, investigators determined the safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%.

From September 2019-October 2021, a total of 356 patients from 46 centers in 17 countries were enrolled in the trial. A total of 316 underwent an implantation attempt. This cohort had a mean age of 53.8±13.1 years, 25.3% were female, the mean BMI was 28.0±5.6 kg/m2, and the mean left ventricular ejection fraction was 38.9±15.4%. Of the 316 who underwent an implantation attempt, the lead was placed successfully in 315 patients and a total of 307 patients underwent defibrillation testing. Regarding the implantation procedure, investigators pointed out implantation was performed by a total of 45 physicians. For these procures, the median time from first incision to final lead position was 35.5 minutes (IQR, 25 to 50), and the median time from first incision to final suture, inclusive of defibrillation testing, was 66 minutes (IQR, 50 to 93).

Upon analysis, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% CI, 96.6%; 

<.001 for the comparison with the performance goal of 88%) and 94.6% were discharged with a working ICD system. Kaplan-Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; 

<.001 for the comparison with the performance goal of 79%). Investigators pointed out there were no major intraprocedural complications were reported.

In the 6-month analysis, 25 major complications were observed in among 23 of the 316 patients included in the trial. Investigators pointed out the success rate of antitachycardia pacing, which was assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). Investigators noted a total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes and 8 systems were explanted without extravascular ICD replacement during the follow-up period, which lasted a mean of 10.6 months.

"While encouraging, these results reflect an early experience, and there is more to be learned with longer follow-up and greater usage," Friedman added, in the aforementioned statement. "The rates of inappropriate shock are higher than with current devices but similar or lower than the early experience with other types of defibrillators, and steps have already been taken to lower it. Additionally, this new device is not for everyone. Patients with previous open-heart surgery were excluded from the study and would not be candidates for this treatment at present."

Efficacy and Safety of an Extravascular Implantable Cardioverter–Defibrillator,

In a pivotal trial presented at ESC Congress 2022, Medtronic's investigational external ICD achieved a defibrillation success rate of 98.7% and met its safety endpoints in a global pivotal trial.

Medtronic's External ICD Meets Safety, Efficacy Endpoints in Pivotal Trial

New data from the VITAL Rhythm Study is highlighting the need for greater emphasis on identification and prevention of 

A prospective cohort analysis of data from the Vitamin D and Omega-3 Trial (VITAL) Rhythm Study by clinicians at the Smidt Heart Institute at Cedars-Sinai Medical Center, the study produced results suggesting women had a lower risk of developing incident AF than their male counterparts, but further analysis controlling for both height and weight suggested females had a 49% greater risk of developing AF than their male counterparts.

“This is the first study to show an actual flip in the risk of atrial fibrillation,” said senior investigator Christine Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute, 

. “In this population of 25,000 individuals without prior heart disease, after adjusting for differences in height, women were at higher risk for developing AF than their male counterparts—upward of 50%.”

Albert, who also led the VITAL Rhythm trial, together with colleagues from the Smidt Heart Institute conducted the current study with the intent of further exploring whether the potential sex differences in incidence of AF observed in previous studies were independent of sex differences in prevalent cardiovascular disease body size, and other risk factors. With this in mind, investigators designed the current study as a prospective cohort analysis of data from the VITAL Rhythm study related to men aged 50 years or older and women aged 55 years or older without a history of AF, cardiovascular disease, or cancer at baseline.

From the study, investigators identified a cohort of 25,119 individuals for inclusion in their analyses. This cohort had a mean age of 67 (SD, 7.1) years, 51% were women, and the median follow-up was 5.3 (IQR, 5.1-5.7) years. During the follow-up period, a total of 900 confirmed incident AF events occurred among the 12,362 men included in the trial and 12,757 women included in the trial, which correlates to event rates of 4.0% and 3.2%, respectively. For the purpose of analysis, sex, height, BMI, body surface area (BSA), and other AF risk factors at study enrollment were used as exposures in the investigator’s multivariable Cox proportional hazards models used to determine associations between sex and AF.

Initial analyses, which adjusted for age and treatment assignment, suggested women were at a lower risk for incident AF than their male counterparts (HR, 0.68 [95% CI, 0.59-0.77]; 

 <.001). Investigators noted this inverse association persisted even after adjustment for race and ethnicity, smoking, alcohol intake, diabetes status, thyroid disease, exercise, and BMI (HR, 0.73 [95% CI, 0.63-0.85]; 

 <.001). Conversely, an increased risk of incident AF was observed for women when height (HR, 1.39 [95% CI, 1.14-1.72]; 

=.001), height and weight (HR 1.49 [95% CI, 1.21-1.82]; 

<.001), or BSA (HR, 1.25 [95% CI, 1.06-1.49]; 

=.009) were substituted for BMI in the multivariate model. Investigators pointed out risk factor associations with incident AF were similar for women and men in stratified models.

“Atrial fibrillation is a disease we want to prevent, regardless of sex or gender,” said Albert. “This informative study is an important step for the medical community to take note of, and begin discussing AFib risk with all patients, whether male or female.”

Sex Differences in Atrial Fibrillation Risk

Despite the notion that men were at greater risk than women for developing AFib, new research indicates women were at a 49% greater risk of developing AFib than their male counterparts of the same height and weight. 

Study Suggests Women More Likely to Develop AFib than Men When Accounting for Height and Weight

Despite advances in care and emphasis on reducing disparities in care, data from a new study suggests socioeconomic- and gender-based disparities still exist when examining outcomes following 

In what investigators are calling the largest, contemporary national study on socioeconomic disparities in cardiac surgery, results of the study, which leveraged data from the Nationwide Readmissions Database, provide insight into these disparities, including an increased risk of 30-day mortality following CABG, SAVR, mitral valve repair, and ascending aorta surgery among female patients and those of lower socioeconomic status.

“Despite advances in cardiovascular surgical care, and health policy initiatives implemented in the last decade to close the disparities gap in cardiac surgery, females and patients of lower median household income quartiles (MHIQs) continue to have worse outcomes following cardiac surgery on a national level,” wrote investigators. “Future research should be focused on root cause analysis for each procedure type, with a greater focus on sex-specific management guidelines and re-evaluating our approach to health policy to combat structural barriers to care.”

Led by Tsuyoshi Kaneko, MD, surgical director of the structural heart program at Brigham, and Women’s Hospital, the present study was conducted with the intent of producing a comprehensive overview of contemporary trends in outcomes following cardiac surgery based on sex and income using data from a nationally representative database. Together with colleagues from Brigham and Women’s Hospital, the Center for Surgery and Public Health, and Boston University School of Medicine, the study used the Nationwide Readmissions Database.

A publicly available, deidentified dataset, the Nationwide Readmissions Database provided investigators with information related to 358,762 patients for inclusion in their study. Of the 358,762 identified for inclusion, 187,296 patients underwent CABG, 109,110 underwent SAVR, 31,009 underwent mitral valve replacement, 5,579 underwent mitral valve repair, and 25,768 underwent ascending aorta surgery. Investigators noted females were the minority for most procedures, with women representing just 22.3%, 32.2%, 37.5%, and 29.7% of those undergoing CABG, SAVR, mitral valve repair, and ascending aorta surgery, respectively.

For the purpose of analysis, investigators included patients aged 18 years or older who underwent CABG, SAVR, mitral valve replacement, mitral valve repair, or repair or replacement of the ascending aorta from 2016-2018. Investigators noted those who underwent concomitant procedures were included within both procedure cohorts and all patients were identified using ICD-10 procedure codes. Using multivariable analysis adjusted for patient characteristics and hospital-level factors, investigators hoped to assess the risk of 30-day mortality based on patient sex and MHIQ. Secondary outcomes of interest for the study included incidence of postoperative complications, including stroke, renal failure, pacemaker implantation, complete heart block, cardiac arrest, major bleeding, and home discharge. Investigators also noted an exploratory analysis was planned to identify characteristics of hospital providing care to determine if significant differences in site of care were associated with disparate outcomes.

In adjusted analyses, results indicated female sex was independently associated with increased 30-day mortality following CABG (aOR, 1.60 [95% CI, 1.48-1.57]; 

 <.001), SAVR (aOR, 1.43 [95% CI, 1.32-1.55]; 

 <.001), mitral valve repair (aOR, 1.84 [95% CI, 1.17-2.87]; 

=.008), and ascending aorta surgery (aOR, 1.19 [95% CI, 1.02-1.38]; 

=.028). Compared to their counterparts in the highest quartile of MHIQ, being in the lowest quartile was associated with an increased risk of 30-day mortality among those undergoing CABG (aOR, 1.40 [905% CI, 1.25-1.58]; 

 <.001), SAVR (aOR, 1.45 [95% CI, 1.27-1.65]; 

 <.001), mitral valve repair (aOR, 1.26 [95% CI, 1.08-1.47]; 

=.004), and ascending aorta surgery (aOR, 1.79 [95% CI, 1.42-2.23]; 

 <.001). Investigators pointed out women were significantly less likely to receive care at urban and academic hospitals for CABG compared to their male counterparts. Additionally, investigators noted those with lower MHIQ received less care at urban and academic institutions for all surgeries.

“Despite advances in the techniques and safety, females and patients of lower 69 socioeconomic status continue to have worse outcomes following cardiac surgery. These persistent 70 disparities warrant the need for root cause analysis,” wrote investigators in their conclusion.

Contemporary Socioeconomic Based Disparities in Cardiac Surgery: Are We Closing the Disparities Gap?

The Journal of Thoracic and Cardiovascular Surgery.

A new study provides insight into contemporary trends in gender- and income-based disparities in 30-day mortality risk following cardiac surgery among patients in the US. 

Gender-, Income-Based Disparities Still Exist in Outcomes Following Cardiac Surgery

An analysis of more than 45,000 patients with 

heart failure with preserved ejection fraction (HFpEF)

 provides clinicians with a snapshot of the patient and clinical characteristics among this patient population in the US.

Presented by Stephen Greene, MD, of Duke University School of Medicine, at the 

, results of the study, which was an analysis of Humedica EMR data from 2010-2020, provide an overview of patient characteristics, treatment patterns, and clinical outcomes across the range of ejection fraction among patients hospitalized with HFpEF.

Designed by Greene and a team of colleagues from St. Luke’s Mid America Heart Institute and Bristol Myers Squibb, the current study was launched with an interest in describing the current landscape of HFpEF in the US. Using Humedica EMR data recorded between January 2010-December 2020, investigators sought to identify patients hospitalized with a primary diagnosis of heart failure and an ejection fraction greater than 40% who were considered hemodynamically stable at admission, without concurrent acute coronary syndrome or end­stage renal disease, and treated with IV diuretic agents within 48 hours of admission. Using this criterion, investigators identified 47,026 individuals for inclusion in their analyses. Using these patients, investigators planned analyses to compare patient characteristics, treatment patterns, and clinical outcomes of these individuals according to ejection fraction range, with ejection fraction ranges defined as 41-49%, 50-59%, and 60% or greater.

Of the 47,026 included in the trial, 13% (n=6335) had an ejection fraction of 41-49%, 40% (n=18,603) had an ejection of 50-59%, and 47% (n=22,088) had an ejection fraction of 60% or greater. Investigators noted the patient characteristics were similar across all 3 groups of ejection fraction ranges, with a median age of 77 years across all 3 groups, the proportion of patients identifying as White ranged from 83-84%, the proportion of patients identifying as Black ranged from 12-13%, median systolic blood pressure ranged from 137-138 mmHg at admission, and median eGFR ranged from 63-64 ml/min/1.73m2 at admission cross the ejection fraction groups.

However, investigators pointed out that, as ejection fraction increased, the proportion of women increased while the median NT-proBNP levels decreased. The lowest rates of coronary artery disease and atrial fibrillation as well as the highest rates of chronic pulmonary disease were observed among those with an ejection fraction of 60% or greater, according to investigators.

With an interest in learning more about the study and potential prescribing practices among this patient population, 

 reached out to Greene, who also serves as an editorial advisory board member for 

, and that conversation is the subject of the following ESC 22 House Call.

This study, “Heart failure across the range of preserved ejection fraction in United States clinical practice,” was presented at ESC Congress 2022.

Stephen Greene, MD, discusses a study he presented at ESC Congress 2022 describing the patient characteristics, treatment patterns, and outcomes among people with HFpEF in the US and based on ejection fraction range at baseline. 

An Overview of HFpEF Characteristics, Treatment Patterns, & Outcomes, with Stephen Greene, MD

 provides evidence demonstrating the cardioprotective benefits of statin therapy far outweigh the potential risk of muscle symptoms reported in previous data.

An analysis of data from 23 trials within the Cholesterol Treatment Trialists’ (CTT) Collaboration, results of the study suggest the excess risk for muscle symptoms observed with statins was less than 1%, with more than 90% of muscle symptoms reported not attributable to 

“For most people taking a statin, any muscle-related symptoms they experience are not likely to be caused by the drug. The known protective effects of statins against cardiovascular disease greatly exceed the slightly increased risk of muscle symptoms. For example, for every 1,000 people taking a moderate intensity statin, the treatment would cause 11 generally mild episodes of muscle pain or weakness in the first year with no significant excess in subsequent years,” said Colin Baigent, BMBCh, director of the Medical Research Council Population Health Research Unit at the University of Oxford,

. “Over a 5-year period, statins typically prevent 50 major vascular events in those with pre-existing vascular disease, and 25 major vascular events in those with no pre-existing vascular disease, with longer treatment yielding larger benefits.”

Although regarded among cardiologists, as well as clinicians in other specialties, as being among the most important and impactful advances in medicine since the 1980s, statins have come under fire for purported side effects, with a potential for muscle symptoms among the most reported side effects of use. Despite the results of N-of-1 studies and other research, concerns surrounding the impact of statin use on muscle symptoms remain.

With an interest in estimating the risk of muscle symptoms with use of statins, investigators designed the current study as a meta-analysis of double-blinded trials with populations of 1000 patients or greater and a minimum follow-up of 2 years within the CTT. From their search investigators identified 23 double-blind trials for inclusion in their meta-analysis. Of these, 19 compared statins against placebo and 4 compared statins against a less intensive statin. From trials comparing statin against placebo, the overall population was 123,940 participants, the mean age was 63 (SD, 8) years, 28% were women, 48% had vascular disease, and the median duration of follow-up was 4.3 years. From trials comparing statin use against a less intensive statin, the overall population was 30,724 participants, the mean age was 62 (SD, 9) years, 26% were women, 100% of had known vascular disease, and the median duration of follow-up was 4.9 years.

In trials comparing statin use against placebo, analysis suggested 27.1% (n=16,835) of the statin group and 26.6% (n=16,446) of the placebo group reported muscle pain or weakness (RR, 1.03 [95% CI, 1.01-1.06]). When assessing reports within the first year, investigators noted a 7% relative increase in reports of muscle pain or weakness among those allocated to statin therapy rather than placebo, which investigators also pointed out corresponded to an absolute excess rate of 11 (95% CI, 6-16) per 1000 person-years. Analysis of the remainder of the follow-up data provided no evidence of any excess risk. According to investigators, only about 1-in-15 reported instances of muscle pain or weakness were attributable to statin therapy.

In trials comparing statin use against less intensive statin therapy, results indicated use of high-intensity regimens, which was defined as atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily, was associated with a larger relative increase in the rate of muscle pain or weakness compared to more moderate intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.

“Muscle symptoms such as pain or weakness were experienced by similar numbers of people in the statin and placebo groups. Statins were not the cause of muscle pain in more than 93% of patients who reported symptoms," Baigent added. "Statin therapy marginally increased the frequency, but not the severity, of muscle-related symptoms. The small excess risk of muscle symptoms occurred principally during the first year after commencing therapy.”

This study, “CTT meta-analysis of the effects of statins on muscle symptoms,” was presented at ESC Congress 2022.

Results of a CTT meta-analysis from ESC Congress 22 detail the excess risk of muscle symptoms observed with statin therapy from more than 20 clinical trials assessing statins against placebo or less intensive statin therapy.

Statin Muscle Symptom Risk Overblown, Does Not Outweigh CV Benefits, CTT Study Shows

Use of P2Y12 inhibitor monotherapy was associated with a lower risk of ischemic events than aspirin monotherapy with no increased risk of bleeding in people with coronary artery disease (CAD), according to the PANTHER analysis.

, the study, which investigators call the most comprehensive meta-analysis to date of individual patient data from RCTs assessing the effects of oral P2Y12 inhibitors against aspirin in patients with CAD, suggests use of P2Y12 inhibitor therapy was associated with a 12% reduction in the primary composite outcome and a number needed to treat (NNT) of 123 to prevent an adverse outcome.

“The relative risk of the primary composite endpoint was reduced by 12% in patients receiving a P2Y12 inhibitor, primarily driven by a 23% relative reduction of myocardial infarction and, secondarily, by numerically but not significantly lower rates of stroke,” said Marco Valgimigli, MD, PhD, deputy chief of interventional cardiology at the Cardiocentro Ticino Foundation, Lugano, Switzerland,

. "The overall risk of major bleeding did not differ, whereas gastrointestinal bleeding and hemorrhagic stroke occurred less frequently in patients receiving a P2Y12 inhibitor than aspirin monotherapy.”

 has contributed to the ongoing situation, questions surrounding aspirin’s longstanding role as a cornerstone in certain cardiovascular prevention settings. As a result of previous trials and observational studies producing mixed results related to optimal choice of antiplatelet therapy for secondary prevention in patients with atherosclerosis, the PANTHER study was designed with the intent of estimating the effects of clopidogrel, prasugrel, or ticagrelor against aspirin on ischemic and bleeding outcomes in patients with established CAD for randomized controlled trials.

A total of 7 trials with 35,752 individual participants from 492 sites across 3 continents were identified for inclusion. These were the ASCET, CADET, GLASSY, CAPRIE, DACAB, HOST-EXAM, and TICAB trials. Of the 35,752 patients included in the overall population of these trials, 11,427 were excluded due to lack of established CAD, 520 were excluded due to premature study termination or occurrence of adverse events before protocol specified comparison of P2Y12 inhibitors and aspirin, and 198 were excluded because they were randomized to a dual antiplatelet therapy regimen.

Of the 24,325 identified for inclusion in the meta-analysis, 12,178 received P2Y12 inhibitor monotherapy and 12,147 received aspirin monotherapy. Of the 12,178 who received P2Y12 inhibitor monotherapy, 62.0% (n=7547) received clopidogrel and 38.0% (n=4633) received ticagrelor. The final analytical cohort had a mean age of 64.3 years, 21.7% were women, and the median treatment duration was 557 days.

The primary efficacy outcome of interest was a composite of cardiovascular death, myocardial infarction, and stroke. Secondary outcomes of interest included incidence of ischemic stroke, hemorrhagic stroke, defined stent thrombosis, definite or probable stent thrombosis, and gastrointestinal bleeding.

Upon analysis, results indicated a primary outcome event occurred among 5.5% receiving P2Y12 inhibitor monotherapy compared with 6.3% among those receiving aspirin monotherapy (HR, 0.88 [95% CI, 0.79-0.97]; 

=.014), with an NNT of 123 patients to prevent 1 adverse event. Analysis of secondary outcomes indicated the risk of major bleeding was similar between both groups, with major bleeding events recognized among 1.2% of those receiving P2Y12 inhibitor monotherapy and among 1.4% of those receiving aspirin monotherapy (HR, 0.87 [95% CI, 0.70-1.09]; 

=.23). Further analysis of adverse clinical events, which was defined as a composite of the primary efficacy outcome and major bleeding, results demonstrated the risk of net adverse clinical events was reduced with P2Y12 inhibitor monotherapy compared to aspirin monotherapy, with such events occurring among 6.4% receiving P2Y12 inhibitor monotherapy and 7.2% receiving aspirin monotherapy (HR, 0.89 [95% CI, 0.81-0.98]; 

=.020). The NNT to prevent 1 net adverse clinical event was 121 patients.

Further analysis of individual endpoints suggested use of P2Y12 inhibitor monotherapy was associated with a lower risk of myocardial infarction compared with aspirin monotherapy, with these events occurring in 2.3% receiving P2Y12 inhibitor monotherapy and 3.0% receiving aspirin monotherapy (HR, 0.77 [95% CI, 0.66-0.90]; 

 <.001). The NNT to prevent 1 myocardial infarction was 136 patients. Additionally, results indicated P2Y12 inhibitor monotherapy was associated with an even greater reduction in myocardial infarction compared to those using low-dose aspirin(HR, 0.59 [95% CI, 0.43-0.79]) rather than high-dose aspirin (HR, 0.85 [95% CI, 0.71-1.01]; 

Investigators also highlighted potential reductions in risk of hemorrhagic stroke (HR, 0.32 [95% CI, 0.14-0.75]; 

=.009), definite stent thrombosis (HR< 00.42 [95% CI, 0.19-0.97]; 

=.041), definite or probable stent thrombosis (HR, 0.46 [95% CI, 0.23-0.92]; 

=.028), and gastrointestinal bleeding (HR, 0.75 [95% CI, 0..57-0.97]; 

=.027) in favor of P2Y12 inhibitor monotherapy compared with aspirin monotherapy.

“The findings from our analysis, which included all available randomized evidence, challenge the central role of aspirin and support a paradigm shift toward single P2Y12 inhibition for secondary prevention in the long-term antithrombotic management of patients with coronary artery disease,” Valgimigli added.

This study, “P2Y12 inhibitor or aspirin monotherapy as secondary prevention in patients with coronary artery disease: an individual participant data meta-analysis of randomized controlled trials,” was presented at ESC Congress 2022.

The PANTHER study, which was a meta-analysis of 7 RCTs comparing P2Y12 inhibitor monotherapy against aspirin for secondary prevention in CAD, suggests use of P2Y12 inhibitor monotherapy was associated with a 12% reduction in risk of the primary composite endpoint, with a 23% relative reduction in risk of myocardial infarction.