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Men with prostate cancer were at a 50% greater risk of developing 

 in the first 5 years after their cancer diagnosis compared to men without prostate cancer, according to recent study in Sweden.

An analysis of data from a population-based cohort study of more than 550,000 men in Sweden, results of the study demonstrate those with prostate cancer were at a 48% greater risk of deep vein thrombosis and a 47% greater risk of pulmonary embolism after adjustment for patient characteristics.

“The magnitude of increased VTE risk among men with prostate cancer seen in our study is lower than that seen for other cancer types as seen in previous studies and is likely attributable to the high proportion of men with localized disease and at low risk of cancer progression,” wrote investigators. “Notwithstanding this, physicians treating men with prostate cancer should be aware of the marked increase in VTE risk in these men, particularly in the first six months following cancer diagnosis, to help ensure timely VTE diagnosis.”

With funding from Bayer AG, the current study was launched by investigators at the School of Cancer and Pharmaceutical Sciences at Uppsala University in Sweden and Bayer AG with the intent of assessing the risk of VTE among those with prostate cancer using data from the Nationwide Prostate Cancer data Base Sweden (PCBaSe). From PCBaSe, investigators identified 92,105 men with a first diagnosis of prostate cancer from 2007-2016 who were matched in a 5:1 ratio by birth year and residential region to 466,241 men without prostate cancer for inclusion in their analyses. Of note, men with T stage 0 or X and those with a previous record VTE were excluded from the study.

The primary outcome of interest for the investigators’ analyses were crude incidence proportion ratios (IPRs) for incidence of VTE in men with prostate cancer compared to men in the control cohort. Investigators pointed out Cox regression was used to calculate the hazard ratios for VTE, with adjustment for confounding factors, which included comorbidities, medication use, and sociodemographic factors.

Among the entire study cohort, 2955 men with prostate cancer and 9774 men without prostate cancer experienced a first VTE event during a median of 4.5 years of follow-up, with deep vein thrombosis accounting for 52% of the total VTE cases. Further analysis indicated the median time from start of follow-up to VTE was 2.5 (IQR, 0.9-4.7) years in the prostate cancer cohort and 2.9 (IQR, 1.3-5.0) years in the control cohort.

When assessing incidence rates, results demonstrate the crude incidence rates of VTE per 1000 person-years was 6.54 (95% CI, 6.31-6.78) in the prostate cancer cohort and 4.27 (95% CI, 4.18-4.35) in the comparison cohort. Further analysis indicated IPRs decreased from 2.53 (95% CI, 2.26-2.83) at 6 months to 1.59 (95% CI, 1.52-1.67) at 5 years. Additionally, in adjusted analyses, results indicated those with prostate cancer were at a 48% greater is of deep vein thrombosis (HR, 1.48 [95% CI, 1.39-1.57])and a 47% greater risk of pulmonary embolism (HR, 1.47 [95% CI, 1.39-1.56]) than their counterparts without prostate cancer.

In the latter portions of their study, investigators pointed out there were multiple limitations within the design of their study to consider when interpreting the results of their work.

“Although we were able to adjust our risk estimates for several patient variables, including comorbidities, medications and sociodemographic factors, lack of information on height, weight, smoking status and alcohol intake may have led to residual confounding,” investigators wrote.

Risk of venous thromboembolism in men with prostate cancer compared with men in the general population: a nationwide population-based cohort study in Sweden

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An analysis of national data from Sweden suggests men with prostate cancer were at a 48% greater risk of deep vein thrombosis and a 47% greater risk of pulmonary embolism compared to their counterparts without prostate cancer.

Prostate Cancer Could Increase Risk of DVT, Pulmonary Embolism by Nearly 50%

Results of the DIPRA study provide evidence supporting the use of distal radial artery access for cardiac catheterization.

Presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2022 Scientific Sessions, results of the study demonstrate distal radial artery access was a safe strategy with a low complication rate, with no significant differences observed for change in hand function of the catheterization hand when compared to proximal artery access up to 30 days post-procedure.

“Recently, we’ve seen growing interest in the distal artery as a unique access for cardiac catheterization,” said lead investigator Karim Al-Azizi, MD, FSCAI, an interventional cardiologist at Baylor Scott and White Health at The Heart Hospital in Plano, Texas, in a statement. “This study serves as reassurance for physicians that should we choose distal radial access over proximal access, it is safe at 30 days and provides minimal risk to hand function.”

Although proximal radial artery access is recommended within guidelines as the preferred method for cardiac catherization, concerns have grown around the potential risk for occlusion of the artery. As a result, interest in the prospect of distal radial artery access has grown. With this in mind, the Distal versus Proximal Radial Artery (DIPRA) trial was launched to assess the differences in procedural success rate and assessment of hand function post-cardiac catheterization.

Conducted at Baylor Scottand White Health, the trial enrolled 300 patients from March 2020-December 2021 who underwent randomization in a 1:1 ratio to undergo cardiac catheterization with distal radial artery access or proximal radial artery access. For inclusion in the study, a patient’s distal radial artery and proximal radial artery needed to be palpable and non-occlusive flow needed to be confirmed via ultrasound. Additionally, distal radial artery and proximal radial artery needed to be sizable to accommodate at least a 5fr sheath.

The primary outcome of interest for the trial, which was assessed using average Z-score methodology, was change in hand function from baseline at 30 days and 1 year. For the purpose of analysis, hand function was defined as a composite of the QuickDASH questionnaire, the hand grip test, and the thumb forefinger pinch test, with the latter 2 measured with hand and pinch grip dynamometers. Secondary outcomes of interest included access feasibility, radial artery patency, and rate of complications.

At the time of analysis, 251 of the 300 patients who underwent randomization had completed their 30-day follow-up, including 126 randomized to distal radial access and 125 randomized to proximal radial access. Investigators pointed out demographics and procedural characteristics, including sheath size used and type of procedure completed were balanced in both groups.

Similar rates of access site bleeding were observed winning the distal radial access arm (0%) and the proximal radial access arm (1.4%) (

=.25). Investigators pointed out 6 patients in the distal radial access arm failed success access and were converted to proximal radial access and a pair of patients randomized to proximal radial access failed successful access. Further analysis revealed radial artery occlusion occurred among 2 patients in the proximal radial access arm and none in the distal radial access arm.

When assessing hand function, investigators found there were no significant differences in the change of and function in the cauterization for the composite score. When assessing individual components of the endpoint, no significant differences were observed between the distal radial access arm and the proximal radial access arm for hand grip (-0 [IQR,-3 to 3.3] vs 0 [IQR, -2.7 to 3.8] kg; 

=.29), pinch grip (-0.3 [IQR, -1.2 to 0.5] vs 0 [IQR, -0.9 to 0.9] kg; 

=.051), and QuickDASH (0 [IQR, -4.6 to 2.3] vs 0 [IQR, -4.6 to 2.3] points; 

This study, “Distal versus Proximal Radial Artery Access for Cardiac Catheterization and Intervention: 30-day outcomes of The DIPRA study,” was presented at SCAI 2022.

Data from an interim analysis of the DIPRA trial suggest distal radial artery access for cardiac catheterization and resulted in no significant differences in hand function compared to proximal radial artery access. 

DIPRA: Distal Radial Access Safe, No Negative Impact on Hand Function vs Proximal Radial Access

New 6-year data from the SAFE-PAD study presented at the 

Society for Cardiovascular Angiography and Interventions (SCAI) 2022 Scientific Sessions

 outline the safety of paclitaxel drug-coated devices compared with non-drug coated devices, with results suggesting no difference in survival was observed between either group up to 6 years after the index procedure.

Created in collaboration with the US Food and Drug Administration to evaluate the long-term safety of paclitaxel-coated devices, results of the SAFE-PAD trial provide evidence of the devices’ safety for femoropopliteal artery revascularization among a real-world population of patients with peripheral artery disease (PAD).

“Our goal is to give patients the most durable treatment possible that will keep them out of the hospital and living their lives. Patients with PAD tend to be of lower socioeconomic status, more likely to be underserved minority populations and often need to travel long distances or take time off work to seek treatment,” said study presenter Eric Secemsky, MD, director of Vascular Intervention at Beth Israel Deaconess Medical Center, Section Head of Interventional Cardiology and Vascular Research at the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, 

Although paclitaxel drug-coated devices have increased in popularity since the approval of the first paclitaxel-coated device in 2012, more recent data has cast doubt on the potential long-term safety and efficacy of these devices, with a 2018 meta-analysis suggesting use may increase mortality. An observational cohort study of Medicare fee-for-service beneficiaries who underwent femoropopliteal artery revascularization with either a drug-coated device or noncoated device, SAFE-PAD enrolled patients aged 66 years or older treated with drug-coated devices or non-drug coated devices beginning in April 2015.

With the intent of assessing whether drug-coated devices were noninferior to non-drug coated devices for all-cause mortality, SAFE-PAD was designed to evaluate risk of mortality with these devices using inverse probability of treatment weighting, with multiple subgroup analyses planned to estimate differences based on risk category, comorbidities, device type, PAD severity, and procedure location.

Overall, 168,553 patients were identified for inclusion in the investigators’ analyses. This cohort included 70,584 rated with a drug-coated device and 97,969 treated with a non-drug-coated device. The overall cohort had a mean age of 77±8 years, 45% were female, 82% were White, 48% were inpatients, 47% presented with critical limb ischemia, 51% had diabetes mellitus, and 65% had ischemic heart disease. Investigators pointed out the median follow-up time was 3.52 (IQR, 1.56-4.70) years, with the maximum follow-up being 6.31 years.

In their primary outcome analyses, which included data from more than 32,000 patients followed for at least 5 years, results indicated there was no significant difference in risk of mortality between those who received a paclitaxel-coated device and those receiving a non-drug-coated device, with weighted cumulative incidences of mortality of 63.6% with non-drug-coated devices and 62.5% with drug-coated devices (

<.0001). Investigators pointed out similar results were observed in subgroups analyses, with no significant increase in risk of mortality observed among those in the low-risk cohort (HR, 0.98 [95% CI, 0.87-1.10]), based on number of total comorbidities (HR, 0.97 [95% CI, 0.94-0.99]), in those with critical limb ischemia (HR, 0.96 [95% CI, 0.95-0.98]), in those without critical limb ischemic (HR, 0.98 [95% CI, 0.96-1.00]), and based on inpatient (HR, 0.98 [95% CI, 0.96-1.00]) or outpatient procedure index (HR, 0.96 [95% CI, 0.94-0.98]).

“Not having access to important treatment options known to reduce the risk of repeat intervention can have a substantial influence on our PAD patients, ultimately impacting their outcomes and quality of life. The findings presented today add to the growing body of evidence showing these devices are safe for use,” Secemsky added.

This study, “Update from the Safety Assessment of Femoropopliteal Endovascular treatment with PAclitaxel-coated Devices (SAFE-PAD) Study,” was presented at SCAI 2022.

Long-term data from the SAFE-PAD trial at SCAI 2022 underlines the noninferiority of paclitaxel-coated devices versus non-drug-coat devices for use in patients with peripheral artery disease.

SAFE-PAD: No Difference in Mortality with Paclitaxel-Coated Devices Up to 6 Years Out

Long-term use of clopidogrel monotherapy was associated with a lower risk of events than aspirin monotherapy beyond the 1-year mark after percutaneous coronary intervention (PCI) in high-risk patients, according to a new analysis of data from more than 7000 patients.

Presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2022 Scientific Sessions, results of the study indicate use of clopidogrel monotherapy was associated with a reduced risk of net adverse clinical events (NACE) and major adverse cardiovascular and cerebrovascular events (MACCE) compared with aspirin monotherapy in patients requiring long-term antiplatelet therapy during the chronic maintenance period of treatment.

“These findings show for the first time clopidogrel monotherapy is associated with reduced risk of long-term NACE and MACCE,” said Hao-Yu Wang, of the Chinese Academy of Medical Sciences and Peking Union Medical College,

. “Our results may have important practical implications for determining the optimal treatment for patients requiring a single antiplatelet drug, either aspirin or clopidogrel, for secondary prevention of ischemic events in high-risk PCI population.”

With the advent of newer therapies and more recent revelations around the effects of aspirin in prevention of cardiovascular disease, numerous studies have been launched to compare the potential real-world safety and efficacy of aspirin monotherapy against newer agents in various patient populations with an indication for antiplatelet therapy. In the current study, Wang and a team of colleagues sought to assess the effects of clopidogrel monotherapy against aspirin monotherapy in patients who had received antiplatelet monotherapy longer than 12 months and were free from ischemic and bleeding events at 12-month post-PCI without extended duration of dual antiplatelet therapy.

For the purpose of analysis, investigators used the prospective Fuwai PCI registry as the data source for their study and identified 8377 consecutive patients at high-risk for both bleeding and thrombosis that satisfied at least one clinical and one angiographic criterion. The primary outcome of interest for the investigator’ was the incidence of NACE from 12-30 months. Secondary outcomes of interest included incidence of MACE and major or clinically relevant major bleeding events, which was classified as BARC type 2, 3, or 5 bleeding.

Of the 8377 identified for potential inclusion, 7392 were event-free after the first year and adherent to DAPT. From this group, investigators identified 5230 patients who received monotherapy, with 1540 receiving clopidogrel monotherapy and 3690 receiving aspirin monotherapy for inclusion in their final analytical cohort. The overall cohort had a mean age of 58.54±10.14 years, 75.8% were male, and 65% received PCI for acute coronary syndrome.

Upon analysis, results suggested incidence of NACE was lower with clopidogrel monotherapy between 12 and 30 months than with aspirin monotherapy, with event rates of 2.3% and 4.4%, respectively (aHR, 0.550 [95% CI, 0.384-0.788]; 

=.001). Secondary analyses revealed clopidogrel monotherapy was also associated with lower risk for MAACE (aHR, 0.447 [95% CI, 0.278-0.718]; 

=.001), as well as lower incidence rates of all-cause mortality (0.6% vs 1.5%; 

=.023), myocardial infarction (0.4% vs 0.9%; 

When assessing safety outcomes, results indicated the difference in risk for BARC type 2, 3, or 5 bleeding was similar between both study arms, with incidence rates of 1.3% with clopidogrel monotherapy and 1.7% with aspirin monotherapy (aHR, 0.738 [95% CI, 0.429-1.272]).

“In this real-world study, clopidogrel has effects on all-cute and cardiovascular mortality, as well as stroke, compared with aspirin monotherapy. Therefore, this strategy might be an effective alternative to aspirin for secondary prevention of cardiovascular disease,” Wang added during his presentation at SCAI 2022.

This study, “Clopidogrel Monotherapy vs. Aspirin Monotherapy for Chronic Maintenance Beyond 12 Months After PCI Among Patients With a High Risk of Ischemic or Bleeding Events

An analysis of data from the Fuwai PCI registry details the incidence of adverse events and risk of bleeding associated with clopidogrel monotherapy versus aspirin monotherapy 12 months post-PCI in high-risk patients.

Clopidogrel Tops Aspirin for Long-Term Antiplatelet Therapy After PCI in High-Risk Patients

The Society for Cardiovascular Angiography and Interventions (SCAI) 2022 Scientific Sessions hit the ground running with the organization’s release of their first comprehensive guideline for management of patent foramen ovale (PFO).

Journal of the Society for Cardiovascular angiography and Interventions 

on May 19, the 15-page document outlines 13 recommendations formulated by a multidisciplinary guideline panel to address 5 PFO clinical scenarios.

“This document represents the first truly rigorous guideline document put forth by the SCAI to lend clarity to a field surrounded by controversy and aid in physician decision making for PFO associated conditions,” said Clifford J. Kavinsky, MD, PhD, MSCAI, chair of the writing group and chief of the Section of Structural and Interventional Cardiology at Rush University Medical Center, 

With an interest in learning more about the guideline writing process and recommendations made within the SCAI’s guideline on management for PFO, 

 reached out to Kavinsky and a transcript of that conversation can be found below.

SCAI Guidelines for the Management of PFO, with Clifford Kavinsky, MD, PhD, MSCAI

What was it like for you to lead the process of creating this historic guideline?

 For a long time, the SCAI has put themselves forward as the voice of interventional medicine. Yet, they have never published a single guideline document about any interventional procedure. So, for them, this is the first time that they are putting forth a rigidly adjudicated guideline document. So, you know, this is very satisfying to me and represents, like 2 years of work leading to this moment.

Can you summarize the top points of this document for our audience?

So, the purpose of this document was to help clinicians, to help third-party payers, and to help policymakers in gaining some clarity around the procedureof PFO closure. Many of the patients who clinicians are actually treating don't fall within the very narrow scope of the large randomized clinical trials. So, the hope of this document was to address many patient selection issues, including some of the more controversial ones.

Now, what are the controversial patient group who may have had PFO-mediated events, but not a stroke? That means patients with refractory migraines, patients who have extensive shunting across their PFO, the so-called orthodeoxia platypnea syndrome patients, patients with thrombophilia, patients who have had a DVT or they may have had a pulmonary embolism, but they've never had a PFO stroke. Also, patients who have had a systemic embolism mediated by a PFL, but not a stroke. All of these are patient populations that were addressed.

Can you discuss the 5 specific clinical situations highlighted in the early portions of the document?

The first one is largely centered around patient subsets who have a PFO and a PFO event but not a stroke. So, patients who have a systemic embolism without a stroke, patients who have like a TIA, patients who have had a DVT or pulmonary embolism, patients with refractory migraine. Those are all patient populations that are not included in a randomized clinical trial.

The second question is the population of patients that really aligns itself with the patients included in the randomized clinical trial. Those are the patients who have a PFO and an ischemic stroke for which no other cause can be found between the ages of 18-60 years. That aligns itself most closely with the FDA labeling and the strong evidence to support PFO closure in these patients. Then, the document goes further and addresses patients over older than 60 years, because randomized clinical trials really only enrolled people up to the age of 60. Well, the panel also supports closing patients over the age of 60. You have had a presumptive PFO-mediated stroke.

There was a lot of controversy centered around patients who have had a presumably PFO-mediated stroke, but it may have occurred years ago. That remains an issue that is unresolved.

The next two questions centered around anticoagulation. Is anticoagulation a reasonable therapeutic option for a patient who's had a PFO stroke, is it a reasonable option is an alternative to PFO device closure?

Although, therapeutically, it may be a reasonable alternative to PFO device closure, it was the recommendation of the panel that these patients should have be a device closure rather than anticoagulation. For the main reason that anticoagulation is tricky. There's a large degree of noncompliance, and we see physicians and patients discontinue their anticoagulation for surgical procedures and other indications. So, you can't ensure uninterrupted anticoagulation and, for that reason, the panel recommended PFO as an alternative rather than anticoagulation.

Then, the next question is patients who have had a PFO-mediated stroke but have a requirement for lifelong anticoagulation for other reasons, such as recurrent pulmonary embolism, recurrent DVT, or thrombophilia. Once again, the panel supports PFO device closure plus anticoagulation, rather than anticoagulation alone, for the same reasons that I've just recited: the issues of noncompliance and interruption of therapy. So, these are sort of the real-life issues that are encountered by the clinician. Many of the patients we get asked to treat do not fall within the narrow scope of inclusion criteria for the randomized clinical trials. So, we try to place some clarity on these other patient populations, and these others their therapies like anticoagulation.

 In your position, how hard is it to really try to put together and put your personal stamp on recommendations that haven't really been examined in clinical trials?

This is why we do make the recommendations. So, for patients who have had a PFO-mediated stroke, for example, the panel recommends full closure rather than anticoagulation. We do get out there and give the guidance, but we have to be honest to say that the supporting data for it is not strong. Therefore, the recommendation is conditional and the conditions of the recommendation are clearly stated.

 What are some of the most immediate areas in need of further research related to PFO?

So, the migraine issue remains a hot controversial topic. There is strong observational data to suggest that PFO closure in these patients ameliorate survivors’ headaches. Yet, the randomized clinical trials to date have been negative. There are ongoing clinical trials and I am hopeful that those will answer this question.

Secondly, the issue of scuba divers with decompression illness. Among these patients, there seems to have beneficial effects of therapy that has not been studied in a randomized trial and everyone could use a randomized trial to clarify.

Then another is patients who have had a PFO-mediated stroke, but it happened to them years earlier. What should we do with those people? Should they and can they be studied in some sort of randomized clinical trial?

Lastly, the issue of how do we treat patients after their PFO closure with medication. There's really no data out there. There's not enough data to even make a conditional recommendation. So that area needs to be studied as well.

Chair of the SCAI's writing group for their 2022 guidelines on management of patent foramen ovale, Dr. Clifford Kavinsky, sits down with Practical Cardiology to take part in a Q&A on the guideline's recommendations and the writing process for the SCAI's first PFO guidance. 

Q&A on SCAI's 2022 PFO Guidelines, with Clifford Kavinsky, MD, PhD

New research presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2022 Scientific Sessions is providing clinicians with insight into contemporary trends in percutaneous coronary intervention (PCI) among patients with cancer.

Using machine learning augmentation and data from the National Inpatient Sample, investigators found the rate of PCI among patients with thrombocytopenia had nearly doubled from 2016 to 2018 and detail the safety of PCI among patients with active, suggesting active cancer was not associated with an increased risk of mortality among patients undergoing PCI in multivariable adjusted analyses.

“Our study aimed to leverage the power of big data and artificial intelligence to provide robust, reliable and relevant results to guide appropriately tailored interventions for cardio-oncology patients,” said senior investigator Dominique J Monlezun, MD, PhD, MPH, adjunct assistant professor at the University of Texas MD Anderson Cancer Center in Houston, Texas, in a statement. “Our hope is to decrease undertreatment among this patient population by ensuring clinicians have reassuring evidence on the safety and efficacy of revascularizations techniques for this specific patient population.”

With the recent advent of cardio-oncology, research into the intersection of cardiovascular disease and cancer has grown in stride with the field itself. Designed with an interest in assessing mortality among patients with thrombocytopenia receiving PCI, the current study is the first nationally representative multi-year cardio-oncology mortality study of thrombocytopenia and coronary intervention and first such study using machine learning augmentation and propensity score.

Check out this article on a recent study examining trends in CV-specific mortality among cancer patients in the US from 1999-2018.

Using data from the 2016-2018 National Inpatient Sample survey cycles, investigators obtained data from 101,521,656 hospitalized adult patients for inclusion in their analyses. This cohort included 6,456,777 patients who had active cancer, which included 396,446 patients with thrombocytopenia. For the purpose of analysis, investigators used propensity scores and multivariable regression modeling to assess differences between patient subgroups.

Upon analysis, results indicated patients with thrombocytopenia and active cancer were significantly less likely to receive left heart catheterization (1.88% vs 5.41%) and PCI (0.48% vs 1.35%) than their counterparts with thrombocytopenia and without active cancer. Further analysis suggested patients with cancer with thrombocytopenia were more likely to have an acute myocardial infarction and to receive intravascular ultrasound but had comparable rates of practical flow reserve and optical coherence tomography than their counterparts with cancer but without thrombocytopenia. In multivariable-adjusted models assessing patients who underwent PCI, investigators found there were no associations observed between active cancer (OR, 0.89 [95% CI, 0.45-1.75]; 

=.738) or any of the other 32 primary malignancies with increased mortality.

"This nationally representative longitudinal study suggests inpatient PCI is relatively safe and is increasing among patients with active cancer regardless of their primary malignancy,” wrote investigators.

This study, “PCI is Safe and Increasing Among Cancer Patients: Nationally Representative Propensity Score Adjusted and Machine Learning Augmented Study of 100 Million Hospitalizations,” was presented at SCAI 2022.

A study from SCAI 2022 details the rate and safety of percutaneous coronary intervention among patients with active cancer and thrombocytopenia in the US from 2016-2018.

PCI Safe, Becoming More Common in Patients with Active Cancer

This article was originally published on 

Data from a trial presented at the American Society of Gene and Cell Therapy (ASGCT) 25th Annual Meeting provides evidence suggesting a novel adeno-associated virus (AAV) vector gene therapy could soon be a reality for patients with congestive heart failure. 

A first-in-human dose-esclatation trial, results highlight data from 3 patients with congestive heart failure (HF) dosed with the AAV vector gene therapy and followed for a year demonstrated clinically meaningful improvements with no safety concerns.

In recent years, heart failure has been identified as an opportunity for gene therapy via gene transfer technology, targeting abnormal intracellular Ca2+ handling and increased protein phosphatase activity.

In results presented at ASGCT, investigators reported on the safety and feasibility of the novel AAV in development by AskBio, AAV2i8 (NAN-101), which is cardiotropic and de-targets the liver to deliver a constitutively active protein phosphatase 1 inhibitor 1 (I-1c), AAV2i8.I-1c. It is delivered via a single antegrade coronary artery infusion, and the study included 3 dose levels.

Twelve-month follow-up data were available for 3 patients in cohort 1 of the first-in-human dose-escalation trial, while follow-up for the 5 patients in cohort 2 is ongoing.

The first cohort included 3 patients with non-ischemic cardiomyopathy and New York Heart Association (NYHA) Class III symptoms of HF. Mean age was 70.0 years, and 2 (67%) patients were male, 1 female. Two patients in cohort 1 are White and 1 is Black.

Additionally, “quantifiable measures of biological activity across a number of parameters, important for assessing HF status, could be detected in patients in cohort 1 in this cardiac gene therapy trial,” the research team reported.

Measures of efficacy included changes in NYHA classification, VO2 max assessed by cardiopulmonary exercise testing, 6-minute walk test, left ventricular ejection fraction (LVEF), and left ventricular regional wall motion.

NYHA classification measured 3 for all 3 patients in cohort 1 at baseline. The difference at 12 months was -1, -2, and -1, for each of the 3 patients, respectively. Compared with baseline LVEF percentage measurements of 37.5, 29, and 34 at baseline, all 3 patients exhibited improvements of 10.5, 22, and 6 percentage points, respectively, at 12-months of follow-up.

One patient in cohort 1 registered a 5% increase in LVEF, while another saw a 10-point decrease on the Minnesota Living With Heart Failure® Questionnaire tool. Additionally, 1 patient in cohort 1 experienced a 1.5 mL/kg/min increase in their VO2 max, while another had a 50-m increase in their 6-minute walk test.

Over the course of a year, 2 patients in cohort 1 experienced 

 1 treatment-emergent adverse event (TEAE), although none were considered related to the study treatment.

The second cohort includes 5 patients for which follow-up is still ongoing. The mean age is 58.8, and 4 (80%) of the 5 patients are male and White.

To date, all 5 patients in cohort 2 have experienced 

 1 TEAE, with 9 series TEAEs reported in 3 patients during the post-intervention period. One of those series TEAEs had a fatal outcome, which was deemed to be due to substance abuse and noncompliance of concurrent medications.

Additionally, 4 of the 5 patients in cohort 2 developed mild transient increases in aspartate transaminase and alanine transaminase 4-12 weeks post-infusion.

A first-in-human phase 1 clinical gene therapy trial for the treatment of heart failure using a novel re-engineered adeno- associated vector

A first-in-human dose-escalation trial of a novel gene therapy suggests use was associated with clinically meaningful improvements in NYHA class and LVEF among patients with congestive heart failure.

AAV Gene Therapy Shows Promise for Congestive Heart Failure

A new set of guidelines from the American Heart Association (AHA) provides clinicians with refined recommendations for management of intracerebral hemorrhages (ICH).

Published on May 17 in collaboration with the American Stroke Association (ASA), the new guidelines provide evidence-based recommendations the organizations hope will replace their most recent guidelines published, which were published in 2015.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures and the underlying disease in small blood vessels,” said guideline writing group chair Steven M. Greenberg, MD, PhD, a professor of neurology at Harvard Medical School and vice chair of neurology at Massachusetts General Hospital, both in Boston, in

Prepared by a volunteer writing group on behalf of the AHA and ASA, the 80-page document is broken down into 9 sections with multiple subsections and cites 649 reference documents. The first update to ICH guidance from the AHA/ASA since their 2015 recommendations, the 9 sections within the guideline are an introduction, general concepts in ICH, organization of prehospital and initial systems of care, diagnosis and assessment, medical and neurointensive treatment for ICH, surgical interventions, outcome prediction and goals of care, prevention, and recovery, rehabilitation, and complications.

Within these 9 sections are significant changes from previous guidance. These include clarification around the lack of benefit seen with compression socks or stockings of any length to prevent deep vein thrombosis, recommendations for use of intermittent pneumatic compression, and updated recommendations for the use of anti-seizure medicines or antidepressants after ICH. Specifically, the guidelines recommend neither of these classes of medications to be used unless a seizure or depression is already present, therefore, they are not advised for most people.

Guideline authors pointed out the guideline had received endorsement from the American Association of Neurological Surgeons, Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Critical Care Society. Additionally, the American Academy of Neurology affirmed the value of this statement as an educational tool for neurologists.To open the guidelines, authors highlighted a list of 10 top take-home messages they chose to highlight from within the new guidelines. An abbreviated version of these messages can be found below.

Summary of Take-Home Messages from 2022 AHA/ASA Guideline for the Management of Patients w/ Spontaneous Intracerebral Hemorrhage.

“There is no easy path to preventing or curing bleeding strokes, yet there is encouraging progress across all aspects of this disease, from prevention to in-hospital treatment and post-hospital recovery. We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Greenberg added, in the aforementioned statement.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association

Published on May 17, the 2022 AHA/ASA guidelines for the management of intracerebral hemorrhage were created with the intent of replacing 2015 guidance with updated evidence-based recommendations. 

American Heart, Stroke Associations Release Updated Guidance for Intracerebral Hemorrhage 

A new study suggests arterial stiffness and not blood pressure or other standard risk factors may be the most effective predictor of type 2 diabetes risk among Chinese patients.

An analysis of more than 11,000 patients from an ongoing, prospective study in China, results of the current study indicate arterial stiffness provided better predictive ability for diabetes than hypertension in multiple sensitivity and subgroup analyses as well as providing a greater incremental effect on the predictive value when added to a conventional risk prediction models with traditional risk factors.

“We were surprised to find that people with increased arterial stiffness were more likely to develop Type 2 diabetes, whether they had high blood pressure or not,” said senior investigator Anxin Wang, PhD, a researcher at the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital in a 

statement from the American Heart Association (AHA)

. “These results provide strong evidence that measuring arterial stiffness may be a better predictor than blood pressure in determining an individual’s future risk of type 2 diabetes.”

With type 2 diabetes posing a significant threat to patient- and population-level health, prevention efforts have taken center stage for providers in endocrinology, cardiology, and internal medicine. Citing previous research suggesting arterial stiffness may be a better predictor of adverse clinical events than blood pressure and a lack of research comparing predictive ability for type 2 diabetes, Wang and a team of colleagues from the Beijing Tiantan Hospital launched the current study to assess the status of hypertension and arterial stiffness, which was measured as brachial-ankle pulse wave velocity (baPWV), in predicting future risk of type 2 diabetes in a community-based population in China.

With this in mind, investigators designed their study as an analysis of the ongoing, prospective Kailuan study. Starting in 2006, the Kailuan study has enrolled more than 100,000 patients and conducted examination surveys every 2 years. Beginning with survey cycle 3 in 2010, patients who consented to join nested studies on vascular health underwent assessments of baPWV. For the current study, investigators included those with at least 1 completed survey from 2010-2014 with synchronized data and no history of diabetes or prediabetes, yielding a cohort of 11,156 patients for inclusion in their analyses.

This cohort had a mean age of 51.53±11.62 years, 57.19% were men, the mean BMI was 24.8±3.40 kg/m2, and the mean baPWV was 1492.83±350.64 cm/s. During a follow-up period lasting a median of 6.16 (IQR, 5.02-7.00) years, a total of 768 incident cases of diabetes were identified by investigators.

Compared to those with ideal vascular function, the greatest risk of diabetes during the follow-up period was observed among those with hypertension and elevated arterial stiffness (HR, 2.42 [95% CI, 1.93-3.03]; 

 <.0001), followed by normotensive patients with elevated arterial stiffness (HR, 2.11 [95% CI, 1.68-2.66]; 

 <.0001), and those with hypertension and normal arterial stiffness (HR, 1.48 [95% CI, 1.08-2.02]; 

 <.0001). Further subgroup and sensitivity analyses yielded similar results.

Additionally, in analyses comparing the predictive value of hypertension and arterial stiffness, 

statistics in a conventional model significantly improved with the addition of arterial stiffness, from 0.690 to 0.707 (

=.0003), but did not significantly improve with the addition of hypertension (

=.0807). Investigators also pointed out the discriminatory power and risk classification of arterial stiffness appeared to be greater than hypertension, with the integrated discrimination improvement for hypertension at 0.28% (95% CI, 0.02-0.40%; 

 <.0001), while the corresponding net reclassification index was 34.59% (95% CI, 27.31-41.87%; 

<0.0001) and 40.48% (95% CI, 33.46-47.50%; 

“This finding that arterial stiffness increases the risk for developing Type 2 diabetes supports our existing understanding of cardiovascular disease and Type 2 diabetes,” said Eduardo Sanchez, MD, MPH, chief medical officer for prevention of the AHA and clinical lead for Know Diabetes by Heart, in the aforementioned statement. “We look forward to future investigations about the mechanisms between arterial stiffness and type 2 diabetes risk.”

Hypertension, Arterial Stiffness, and Diabetes: a Prospective Cohort Study

An analysis of data from more than 11,000 patients in China suggests arterial stiffness could be a better predictor of type 2 diabetes risk than other traditional risk factors, such as hypertension. 

Arterial Stiffness a Better Predictor of T2D Risk than Blood Pressure in Chinese Patients

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC: 

There are a lot of considerations in managing patients with atrial fibrillation. We want to think about rate control vs rhythm control. A lot of randomized clinical trial data can help guide us. It’s interesting, the newer data are a bit stronger for rhythm control than older data that suggested rate control is as good as rhythm control. But now that we’re getting better with rhythm control, safer antiarrhythmics than some of the older ones, better knowledge of how to use them and what doses are better, that has enhanced the ability to deliver rhythm control. In particular, atrial fibrillation ablation—that is, procedural ablation—has gotten a lot better and safer. In carefully selected patients, there’s a role for everything. For some patients, it may be reasonable just to control their rate. If they’re asymptomatic and happy, leave them alone. For patients who continue to have symptoms despite rate control, or if their rate control at rest is sufficient but rate control with exercise isn’t, more rate control could help. Rhythm control might also be useful in that. Rhythm control might be antiarrhythmic medications, procedural care, procedural care if antiarrhythmic medications fail. There are a lot of options.

It’s important to know that with antiarrhythmic drugs, some are better in patients with heart failure, but some are much worse in patients with heart failure. For many drug interactions, you might want to consult a cardiac electrophysiologist or pharmacist if you’re getting into polypharmacy with a number of the atrial fibrillation drugs. Nonetheless, there are a lot of options these days in not only rate control but also potentially rhythm control.

The other important thing to consider beyond that aspect is anticoagulation, because the biggest risk from atrial fibrillation is stroke. It’s very important that the majority of these patients get anticoagulated. Look at things like the CHA2DS2-VASc score. You can use that. There are online calculators. Many electronic health records incorporate automatic calculation of the CHA2DS2-VASc. In patients with very low scores, perhaps anticoagulation can be avoided. But the vast majority of patients with atrial fibrillation should get anticoagulated. It’s not just if they have sustained atrial fibrillation. Even patients with intermittent or paroxysmal atrial fibrillation, barring contraindications, should be anticoagulated.

Contraindications get tricky. We used to say, “If the patient falls a lot, don’t anticoagulate them.” But studies have shown the patient needs to fall many times before the benefits of anticoagulation are outweighed by those risks. Other than the most frail patient, one who’s had previous head trauma with bleeds into their brain, the majority of patients—even older ones—should be anticoagulated. In fact, it’s that older patient who’s at risk for thromboembolic stroke that could be disabling or fatal. There is vast underutilization of anticoagulation. We want to be much more thorough in identifying patients who could benefit from anticoagulation if they got atrial fibrillation.

The agents of choice are clearly DOACs [direct oral anticoagulants] or NOACs [novel oral anticoagulants], the non–vitamin K oral anticoagulants. I guess they’re not novel anymore. In fact, the majority of prescriptions for new cases of atrial fibrillation worldwide, not just the United States, are NOACs. That’s because they reduce intracranial hemorrhage risk vs even good warfarin use. Even when the INR [international normalized ratio] is well controlled, the NOACs beat warfarin for intracranial hemorrhage and are at least as efficacious. They’re safer, at least as efficacious, and easier to use than warfarin, without any need for routine monitoring. That’s the standard of care worldwide. There are some exceptions. If patients have mechanical heart valves, we still would use warfarin. There’s some debate that if they’ve got antiphospholipid antibodies or are in hypercoagulable states, warfarin might be better. There are still subgroups where warfarin has a role if they also have atrial fibrillation. But most atrial fibrillation patients need to be anticoagulated. Most atrial fibrillation patients should be receiving a NOAC.

Make sure to check the label and dose appropriately. Don’t underdose. A number of NOACs have lower-dosing regimens. Don’t use them unless the label supports the lower dosing. Be cognizant of the kidney function, in particular, and in some cases the weight, depending on the NOAC. Kidney function can fluctuate, especially in older patients who might necessitate a change in the NOAC-dosing regimen depending on the NOAC. Check the label of whatever NOAC you’re using, dose appropriately, and depending on the particular NOAC, factor in kidney function for sure and in some cases age and weight. If there are any questions beyond the label, ask your pharmacist. This is a place where dosing error, underdosing and accidental overdosing, can occur. Be vigilant for those possibilities, and try to avoid them.

Videos

Dr Deepak L. Bhatt shares considerations for managing patients with atrial fibrillation, including rate control vs rhythm control and the use of anticoagulation methods.

Approaching the Management of Atrial Fibrillation

A patient in her mid-70’s with a history of hypertension presents to the hospital with intermittent palpitations as well as worsening bedsores. She saw her doctor and had an abnormal EKG, which triggered a referral to an electrophysiologist but had palpitations again today lasting about 20 minute so came to the ER. She did not check her heart rate during the episode and denies syncope, chest pain, SOB, fever, cough, or other complaints.

Vital signs are normal. The physical exam is also normal.

Computer Read: NSR with PACs, nonspecific ST and T waves

Our latest cardiology case report features a woman in her mid-70s with a history of hypertension presenting to the hospital with intermittent palpitations as well as worsening bedsores. Check out the EKG and determine the correct diagnosis!

Cardiology Case Report: Bedsores and Palpitations

New research from a team of investigators in Europe suggests hormonal changes during menopause could explain up to 10% of the increase in LDL-C associated with the transition to menopause among aging women.

An analysis of data from more than 200 women in a prospective study, results of the study suggest the hormonal shift in 17β-oestradiol (E2) and follicle-stimulating hormone (FSH) levels among women transitioning from perimenopause to early postmenopause was associated with proatherogenic circulating metabolome alterations, with these metabolite shifts were partially ameliorated with hormone replacement therapy (HRT).

“Menopause is unavoidable but it is possible that the negative metabolite shift can be diminished by eating healthily and being physically active,” said study investigator Eija K. Laakkonen, PhD, associate professor of Gerontology and Public Health of the University of Jyväskylä in Finland,

. “In particular, women should pay attention to the quality of fat in their diet and getting sufficient exercise to maintain cardiorespiratory fitness. HRT is an option that women should discuss with healthcare providers at this point in their lives.”

With previous data establishing the menopausal transition as a period often associated with a negative change in cardiometabolic health biomarkers, Laakonen and a team of colleagues sought to further explore these associations beyond clinical biomarkers using metabolomics to assess the effect of the menopausal transition on circulation metabolite. Using data from the Estrogenic Regulation of Muscle Apoptosis (ERMA) prospective cohort study, investigators obtained data related to a cohort of 234 Finnish women followed through the menopause transition who kept a menstrual diary during follow-up and underwent laboratory assessments of FSH levels every 3 or 6 months until early postmenopause. After the application of further inclusion criteria, which included not reaching menopause, unknown menopause status, and inconsistent HRT use, a total of 218 participants were identified for inclusion in metabolomics analyses. Of these 218 women, 35 started HRT during the study.

The mean age of participants at first measurement was 51.7 (SD, 1.9) years and the median follow duration was 14 (IQR, 8-20) months, with an overall range of 4 months to 3.5 years. Of the 35 women who started HRT during the study, 27 received oral therapy and 8 received transdermal HRT.

Investigators included a pair of exploratory analyses in their study. The first metabolomic analysis assessed the direct and indirect associations, measured via body fat percentage change, between the menopausal hormonal shift and metabolite changes in the 183 women experiencing natural menopause using latent change score modeling. The second analysis assessed the association of HRT initiation during follow-up with the metabolite measurements was studied in the entire study cohort using menopausal status and HRT interaction as the exposure.

In adjusted analyses, the concentration of ApoB (0.17 SD [99.5% CI, 0.03 to 0.31), very-low-density lipoprotein triglycerides (0.25 SD [99.5% CI, 0.05 to 0.45]) and particles (0.21 SD [99.5% CI, 0.05–0.36]), LDL-C (0.17 SD [99.5% CI, 0.01 to 0.34]) and particles (0.17 SD [99.5% CI, 0.03 to 0.31]), HDL triglycerides (0.24 SD [99.5% CI, 0.02–0.46]), glycerol (0.32 SD [99.5% CI, 0.07 to 0.58]) and leucine increased (0.25 SD [99.5% CI, 0.02 to 0.49]). Additionally, citrate (−0.36 SD, CI −0.57 to −0.14) and 3-hydroxybutyrate concentrations decreased (−0.46 SD, CI −0.75 to −0.17).

Further analysis demonstrated most metabolite changes were associated with the menopausal hormonal shift, which explained 11% and 9% of the LDL-c and particle concentration increase, respectively. Investigators also pointed out menopausal hormone therapy was associated with increased medium-to-large HDL particle count and decreased small-to-medium LDL particle and glycine concentration.

“This study links hormonal changes during menopause to metabolic alterations that promote heart disease. Previous studies did not confirm menopausal status with hormone measurements, meaning that they could not differentiate menopausal effects from aging. Our results should be interpreted with caution, since the links with sex hormones and HRT were found in exploratory analyses and need confirmation,” added Laakkonen.

Menopause modulates the circulating metabolome: evidence from a prospective cohort study

European Journal of Preventive Cardiology.

Metabolomic analyses of data from more than 200 women from a team of European investigators detail the impact of hormonal shifts associated with the transition to menopause on cardiovascular risk.

Hormone Shift in Menopause Contributes to Cardiovascular Risk in Aging Women

The US Food and Drug Administration (FDA) has granted approval to Onyx Frontier drug-eluting stent (DES) for treatment of patients with coronary artery disease, according to 

Announced on May 13, Onyx Frontier DES represents the latest iteration of Medtronic’s drug-eluting coronary stent system and the approval provides Onyx Frontier with the same clinical indications as Resolute Onyx, including the most recent approval for patients that are at high risk of bleeding who may benefit from a DAPT duration as short as one month.

"The new Onyx Frontier DES, with its enhanced deliverability, will continue to help interventional cardiologists treat complex coronary cases and larger ranges of vessel sizes more efficiently," said Azeem Latib, MD, section head of interventional cardiology and medical director of structural heart interventions at Montefiore Medical Center in New York City, in the aforementioned release. "Delivering safe and effective outcomes to our patients is our number one priority. It's important that physicians have access to tools like the Onyx Frontier DES that can allow them to efficiently achieve those outcomes."

According to Medtronic, the Onyx Frontier DES uses the same stent platform as the Resolute Onyx DES, but is designed with multiple changes, including increased catheter flexibility, an innovative dual-layer balloon technology and a lower crossing profile, which contributed to a 16% improvement in deliverability compared to Resolute Onyx. In their release, Medtronic noted the Onyx Frontier will be available in 2.0 mm sizes as well as 4.50-5.00 mm sizes that can be expanded to 6.00 mm.

The release from Medtronic also noted the Onyx Frontier DES is currently pending CE Mark from the European Medicines Agency.

"The Onyx Frontier DES FDA approval is a very important milestone for Medtronic's Coronary business and demonstrates our commitment to interventional cardiologists by providing best-in-class products," said Jason Weidman, senior vice president and president of the Coronary and Renal Denervation business at Medtronic, in the release. "The Onyx Frontier launch also correlates directly to Medtronic's commitment to engineering. The team built upon the design and clinical successes of the Resolute Onyx DES and has continued to evolve proven DES technology to further address the needs of physicians. We look forward to continuing the pursuit of innovation each day."

Announced on May 13, the Onyx Frontier DES carries the same clinical indications as Medtronic's Resolute Onyx DES and will be available in 2.0 mm sizes as well as 4.50-5.00 mm sizes that can be expanded to 6.00 mm. 

Onyx Frontier Drug-Eluting Stent Receives FDA Approval for CAD

The old adage “time is of the essence” rings true when it comes to reducing cardiovascular risk among patients with type 2 diabetes, according to the results of a new study.

Results of the study demonstrate achieving ideal glycemic control within the first 12 months of diagnosis was associated with an improved prognosis when assessing risk of cardiovascular events among patients with type 2 diabetes, with those achieving glucose control in the first year reducing their risk of cardiovascular events by 25% while those who failed to address elevated HbA1c in the first 12 months experiencing a 21% increase in risk of cardiovascular events and those with the greatest HbA1c variability increasing their risk by 51%.

"The conventional wisdom has been to slowly and steadily treat type 2 diabetes with diet and medicine dose-escalation over years - the period over which it took people to reduce their sugar levels after diagnosis was thought less important for major vascular protection. However, our observational study suggests that getting blood levels under control quickly – within the first 12 months after diagnosis – will significantly help reduce cardiovascular events,” said study investigator Martin Whyte, BSc, PhD, a reader in Metabolic Medicine at the University of Surrey, 

Citing data from the UK Prospective Diabetes Study that showed early glycemic control was associated with a reduction in macrovascular events, Whyte and team of colleagues sought to assess whether early glycemic control after a diagnosis of type 2 diabetes might reduce the risk of major adverse cardiovascular disease events.With this mind, investigators sought to conduct a retrospective cohort analysis of adults with type 2 diabetes from the University of Surrey’s Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database, which contains primary care records from 1,595,170 people registered from 164 practices in England.

For inclusion in the investigators’ analyses, individuals needed to be newly diagnosed with type 2 diets on or after January 1, 2005, be aged at least 25 years or older at the time of diagnosis, and have HbA1c measurements at both diagnosis and after year 1 plus 5 or more measurements thereafter. For the purpose of analysis, 3 glycemic bands were created: group A, B, and C. These groups were defined as having HbA1c levels of less than 7.5%, 7.5-9.0%, and 9.0% or greater, respectively. Movement between bands from diagnosis to 1-year were used as exposures for the investigators’ analysis. The primary outcome of interest was the risk of major adverse cardiovascular events at 1-year post diagnosis, which investigators assessed using time-varying Cox proportional hazards models that included first-year transition and glycemic variability score.

Overall, 26,180 individuals were identified for inclusion. This cohort was 43.9% were female, had a median follow-up time of 1583 (IQR, 987-1737) days, a mean BMI of30.7±6.4 kg/m2, and, at the time of data extraction, a mean age of 68.7±12.6 years. Initial analysis indicated 48% of individuals began in band A and maintained that status, 16.1% improved from band C to band A, and 14.6% improved from band B to band A from diagnosis to 1-year. Investigators pointed out 7% of individuals began in band A but moved to band B or band C during the first 12 months.

Among the 26,180 patients included in the study, 4179 MACE events were recorded prior to diagnosis of type 2 diabetes and an additional 1457 events were identified in the first 12 months after diagnosis. Investigators also noted 2300 events occurred beyond the 1-year mark.

Compared to those who maintained band A status from baseline to 1-year, those who transitioned from band C to band A during the first year had a reduced risk of major adverse cardiovascular events (HR, 0.75 [95% CI, 0.60-0.94]; 

A retrospective analysis of more than 25k patients with type 2 diabetes details the impact achieving early glycemic control can have on the risk of cardiovascular disease events among these patients. 