Aaysha Cader, MD, MRCP – The Early Career Voice

Aaysha Cader, MD, MRCP is an Assistant Professor of Cardiology at Ibrahim Cardiac Hospital & Research Institute, Dhaka, and is currently pursuing a part-time MSc in Clinical trials at the University of Oxford. She has a special interest in interventional cardiology, acute coronary syndromes, and heart disease in women. She is a World Heart Federation Emerging Leader and a co-founder of the Global Women in Cardiology (WIC) - Early Career collaboration. You can follow her on twitter: @aayshacader

The PATENS Trial: What does this mean for nitroglycerin in reducing radial artery occlusion?

April 18, 2022April 18, 2022 Aaysha Cader, MD, MRCP

Written by Aaysha Cader, MD, MRCP and Saidur Rahman Khan, MD, PhD

Ibrahim Cardiac Hospital & Research Institute, Dhaka, Bangladesh

Transradial access (TRA) is gaining increasing popularity for diagnostic and therapeutic interventions globally. Radial Artery Occlusion (RAO) however, is the most frequent complication of transradial access. An occluded radial artery precludes its future use for future catheterization procedures, as a conduit in coronary artery bypass grafting or for arteriovenous fistula creation.¹

A number of randomized controlled trials have tested different strategies to reduce RAO, particularly in recent times. Vasodilators such as nitroglycerin have been used prophylactically to reduce radial artery spasms. By virtue of their anti-inflammatory effects and reduction of intimal hyperplasia, they could also enhance regional arterial flow, facilitating patent hemostasis.

A previous randomized trial of intraarterial nitroglycerin vs placebo given through the sheath at the end of the procedure showed a reduction of RAO at 24 hours.² In the PATENS trial, the investigators used an interesting 2×2 factorial design to evaluate whether nitroglycerin administration either at the beginning or at the end of a TRA procedure, might prevent RAO.³

This trial, recently and published in JACC: Cardiovascular Interventions, was a multicentre, randomized, double-blind, 2-by-2 factorial design trial of all-comer patients undergoing TRA for either diagnostic or therapeutic coronary intervention via either 5 or 6 French sheaths. The trial compared the superiority of 500 µg nitroglycerin (intervention) versus placebo. The 2-by-2 factorial design entailed that the patient be randomized at two-time points:

early: immediately after access was obtained and upon sheath insertion; and once again
late: after completion of the procedure and just before sheath removal.

Intra-arterial heparin (5,000 U) was given through the radial sheath to all patients. In cases of PCI, additional heparin was used (total 100 IU/kg). Minimal pressure patent arterial hemostasis was achieved by a pneumatic compression device.

The primary outcome was early RAO (at 24 hours): This was evaluated by duplex Doppler Ultrasound (DUS) within 24 hours of removal of the compression device by operators who were blinded to the randomization allocation.

The secondary outcome was late RAO, which was assessed at 30 days by DUS for recanalization among all those patients with early RAO.

The study was powered at 80% to test superiority for the primary endpoint with an estimated 40% reduction of RAO incidence for the intervention, at a significance level of 5%, with an expected incidence of 7.7% of early RAO in the comparator arm. A possible 0.3 interaction was anticipated considering factorial design. The sample size was estimated at 2,040. Accordingly, 2,040 patients underwent transradial catheterization at 3 centers in Brazil, 1020 in each arm at each randomization. The mean age was 61.7 years; 37.9% were women. 75.2% of procedures were diagnostic coronary angiographies. 25.6% of patients had prior radial catheterization. 60.6% had 5 F radial sheaths, while 39.4% had 6 F sheaths.

There were no significant differences in the primary outcome, RAO at 24 hours between nitroglycerin early use and placebo (2.5% vs 2.3%; P = 0.664); RAO was also not different between nitroglycerin late use and placebo (2.3% vs 2.5%; P = 0.664). Furthermore, a preliminary test for interaction among the factors showed no statistical significance (P = 0.665). In the multi-arm analysis, the combined use of nitroglycerin, early and late, did not show benefit compared with placebo at either of the time points examined.

Although not reaching statistical significance, numerically more radial artery spasm was noted among those who did not receive nitroglycerin pre-procedure (early group): 13.4% vs 10.8% (p=0.06). Needless to say, caution must be exercised when interpreting such ‘trends’.

At 30-day follow-up, recanalization by the antegrade flow on DUS was 30.6%, with no difference between groups. Subgroup analysis showed no benefit from nitroglycerin use in any of the evaluated subgroups, which included sex, age, operator experience, procedure type, sheath size, sheath to artery ratio, and spasm. It has not been mentioned if these subgroups were pre-specified.

Among the 24.8% of patients who underwent PCI (11.6% elective, 13.2% ad hoc), only 1.8% had RAO, with no significant difference with nitroglycerin use compared with placebo at either of the 2-time points.

The presence of clinical spasm (OR: 3.53; 95% CI: 1.87-6.66; P < 0.001) and access achieved with more than a single puncture attempt (OR: 2.58; 95% CI: 1.43-4.66; P = 0.002) were significant independent predictors of 24-hour RAO by multivariable logistic regression analysis.

Overall, the results of this factorial design trial indicate that the intraarterial use of nitroglycerin given before or after puncture does not reduce the risk of early RAO after TRA. The investigators included an all-comer population, of whom 24.8% underwent PCI, including ad hoc PCI, lending greater generalizability to the findings. Also, both 5 and 6 F sheaths were allowed, although the majority were indeed 5 F.

Two prior randomized trials have investigated the impact of nitroglycerin in RAO. Dharma et al, randomized 1704 patients 1:1 in 3 global centers to receive either 500µg intra-arterial nitroglycerin or placebo at the end of the radial procedure and before sheath removal.² Nitroglycerin reduced the risk of RAO at 24 hours, as compared with placebo (8.3% vs. 11.7%; odds ratio, 0.62; 95% confidence interval (CI), 0.44–0.87; P=0.006).²

In a smaller RCT, Chen et al. randomized 188 patients to receive subcutaneous injection of 0.5 mL 0.1% nitroglycerin or a placebo prior to sheath insertion.⁴ After sheath insertion, the subjects received an intra-arterial injection of 200 µg nitroglycerin and 3000 IU unfractionated heparin. RAO was substantially lower in the nitroglycerin-treated group versus placebo (5.4% versus 14.4%; P=0.04).

In comparison to both of these trials, very low levels of RAO were recorded in both groups in the PATENS trial, which could be partially explained by the application of contemporary best practices for RAO prevention.¹ These include patent hemostasis, the use of intra-arterial heparin in higher doses (5000 U), and potentially, more increased anticoagulation among the PCI (24.8%) patients. Neither of the previous trials mentions a patent hemostasis protocol in their methods,^2,4, and indeed the use of a patent hemostasis protocol may have taken away the RAO-prevention advantage of nitroglycerin by improving regional flow.

The percentage of women enrolled in this trial was 37.9%. Particularly as female sex is a risk factor for RAO,¹ they should also be enrolled in greater proportions. Furthermore, a pre-procedural DUS with measurements of radial artery diameters may have allowed for further analyses of predictors of RAO and spasm and assessment of nitrates response according to baseline radial artery diameters. Reporting of radial artery spasms in all trials assessing RAO, may also be a useful factor when interpreting trial findings.

So, what are the implications of this trial in clinical practice? In many parts of the world, best practice for RAO prevention is not entirely adhered to, particularly patent hemostasis, and thus, there may still be a role for nitroglycerin role for nitroglycerin in RAO prevention. Also, the fact that spasm was numerically lower in those who received nitroglycerin pre-procedure and that spasm was indeed an independent predictor of RAO is additional food for thought. Furthermore, this trial only looked at the effect of nitroglycerin: there remains scope for randomized evidence in the use of other spasmolytics (e.g. verapamil and diltiazem) as both a strategy to reduce RAO, and to prevent spasms. And finally, any future RAO trial design and planning should also account for the low incidence of RAO in presence of contemporary best-practice.

References

Bernat I, Aminian A, Pancholy S, Mamas M, Gaudino M, Nolan J, et al; RAO International Group. Best Practices for the Prevention of Radial Artery Occlusion After Transradial Diagnostic Angiography and Intervention: An International Consensus Paper. JACC Cardiovasc Interv. 2019;12(22):2235-2246.
Dharma S, Kedev S, Patel T, Kiemeneij F, Gilchrist IC. A novel approach to reduce radial artery occlusion after transradial catheterization: postprocedural/ prehemostasis intra-arterial nitroglycerin. Catheter Cardiovasc Interv. 2015;85:818–825.
da Silva RL, de Andrade PB, Dangas G, Joaquim RM, da Silva TRW, Vieira RG, et al. Randomized clinical trial on prevention of radial occlusion after transradial access using nitroglycerin (PATENS trial). J Am Coll Cardiol Intv. 2022,00(00):000-000.
Chen Y, Ke Z, Xiao J, et al. Subcutaneous injection of nitroglycerin at the radial artery puncture site reduces the risk of early radial artery occlusion after transradial coronary catheterization. Circ Cardiovasc Interv. 2018;11(7):e006571.

Top tips for getting involved in editorial boards – Insights from #QCOR21

June 23, 2021June 18, 2021 Aaysha Cader, MD, MRCP

QCOR Summer Meet Up 2021 was a fabulous one-day event of networking, mentorship and sharing experiences. There was something for everyone across the spectra of careers, especially for early and mid-career physicians and researchers in the cardiovascular outcomes space.

The sessions were interactive, with opportunities for questions to be fielded to expert moderators. One such meeting with doctors Ann Marie Navar, MD, PhD and Dennis Ko, MD, FRCPC, MSc on How to get invited onto editorial boards had some superb insights, a few of which I’ve penned down on this blog.

Write well and publish: Editors look at your prior academic publishing footprint. This can be any previous writing experience: manuscripts, book chapters, publications, even blogging work – that proves you can write and can get your name out there. If not original science, one can always write editorials, viewpoints or comments to scientific articles in the form of correspondence.

Be a good reviewer: The first step to joining an editorial board and indeed becoming a good editor, is to become a good reviewer. Advantages to reviewing articles for journals are many – good reviewers are eventually recognised, and when known as a high-quality reviewer, even considered for a position on the editorial board when there is an opening. A well-done review also affords the potential to be invited to write an editorial on the content reviewed. Further, some journals let you self-nominate to write an editorial – including an accompanying sentence or two on why you should be writing it is a good idea.

Top tips for writing a good review: Journals look for someone who understands critical appraisal, especially methodology and bias in the outcomes world. A good review is a structured, concise review. It is not the reviewers’ job to nitpick every detail or re-write the manuscript for the authors. It’s important to assess the integrity of the paper for its scientific value. Brevity is key, with a focus on what the paper is about, if indeed it is worth publishing, what is novel or interesting about it, and how it will add to the literature. Comments on major flaws if any, are absolutely necessary, as well as priority of publication. Be professional in comments to the authors, as an overly negative/ harsh attitude is not well-received.

Good reviewing etiquette: Too many requests for reviews can sometimes be overwhelming. Even so, it’s not the best idea to decline a review request from a top tier journal or one with a high impact factor, as these might constitute missed opportunities. It’s also good etiquette to review for a journal in which you’ve just published. However, if you absolutely do not have the bandwidth, decline with good reason and mention them in the checkbox. Having agreed to review an article, it should be done expeditiously. Speedy reviews are efficient and always appreciated, as they help speed up turnover and clear article backlogs.

Seek feedback: A great way to self-assess one’s reviews as a junior reviewer, is to read more senior reviewers’ comments on the same manuscript, as well as the editors’ comments. One can also reach out to the associate editors for suggestions on improvements, who might be able to provide feedback, time-permitting.

Watch out for calls: An increasing effort is being made to improve diversity in editorial boards, with open calls to fill vacant positions. Such openings in editorial boards are often advertised on social media, or via emails sent to society member mailing lists. For more junior researchers, some journals offer editorial internships or assistant reviewer programs, with assigned associate editors that provide feedback on reviews. This is a great place to start, and depending on performance, might eventually lead to a permanent spot on the editorial board too.

Networking and reaching out: And finally, a combination of good skills, clever presentation of one’s abilities, and good networking might just be what lands you your next opportunity. Reach out to peers, mentors and sponsors for support and opportunities. Let your work and your name be known, so that when a suitable opportunity avails itself, you are invited to be a part of it.

I’d like to thank doctors Ann Marie Navar, MD, PhD and Dennis Ko, MD, FRCPC, MSc for sharing these really insightful tips on good reviewing, scientific writing and eventually getting invited to editorial boards. #QCOR21 continues at Scientific Sessions which will be held on November 13–15, 2021 at Boston, MA.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

Trends in COVID-19 in-hospital mortality: Insights from the AHA COVID-19 CVD registry

June 14, 2021June 9, 2021 Aaysha Cader, MD, MRCP

Information on the survival trends of hospitalized COVID-19 patients is important for physicians to identify trends and track the efficacy of hospital-based care in real-world practice. The American Heart Association’s (AHA) COVID-19 Cardiovascular Disease (CVD) Registry was put in place in April 2020 with the objective of improving nation-wide surveillance of hospitalized patients with COVID-19.¹ Early data derived from this registry were presented at scientific sessions #AHA20 last year. This blog summarizes a more recent analysis by Gregory A. Roth and colleagues, looking at trends in patient characteristics and COVID-19 in-hospital mortality in the United States during the pandemic.²

This retrospective study published in JAMA Network Open included 20 736 hospitalized patients from the AHA COVID-19 CVD registry at 107 hospitals in 31 states. Undertaken as part of the Global Burden of Disease Study, the objective was to quantify changes in in-hospital mortality rates during the first 9 months of the pandemic, and understand if any observed changes were associated with differences over time in the characteristics of presenting patients. The data were analyzed to show comparative trends across 4 periods in 2020: March and April; May and June; July and August; and September through November.

There was a gradual decline in the numbers of admitted patients in the registry, with 11 901 patients admitted in March or April, down to 2010 patients in September through November. In terms of the patient demographics, 45.9% were women, the proportion of which slightly increased over time. The mean age was 61.2 ±17.9 years which decreased from March -April through September-November. 58.4% of patients were hypertensive. 35% were diabetic, and 18.3% had pulmonary disease. The mean BMI was in the obese range (30.8 ± 8.5) and increased a small amount through November.

Almost a quarter of patients were receiving supplemental oxygen on admission. This proportion increased from 23% in March – April to 35.9% in September through November. This was despite the presence of interstitial infiltrates on admission decreasing from 70.7% of patients to 60.8% during the corresponding periods. In contrast to supplemental oxygen, however, the use of mechanical ventilation decreased substantially from 23.3% to 13.9% during the same periods. The use of glucocorticoids and remdesivir increased substantially, potentially reflecting the emergence of randomized evidence of its efficacy during that time and the US Food and Drug Administration (FDA) announcement of remdesivir emergency use authorization on May 1, 2020.³ The mean duration of hospital stay also showed a reduction from 10.7±12.1 days to 7.5 ± 6.8 days.

A total of 3271 in-hospital deaths recorded from March through November 2020, corresponding to overall in-hospital mortality of 15.8%. In-hospital mortality rates declined as time progressed, with 19.1% in March-April, 11.9% in May-June, 11% in July-August, and 10.8% in September- November. Adjusted odds for in-hospital death were also significantly lower for all 3 later time periods studied, compared with March-April. Increasing age was the factor most strongly associated with death, with the figure depicting the adjusted odds ratios across different age groups [Figure 1]. Male sex, BMI > 45, and presences of comorbidities, specifically cancer, cerebrovascular disease, diabetes, and heart failure were independently associated with in-hospital death.

The greatest reduction in the in-hospital mortality rates occurred between March and May 2020, with high mortality rates falling by a massive 38% from March and April 2020 by May and June, followed by a modest further decrease by November. Notably, this difference in mortality rates persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity. In the face of only minor changes in the characteristics of admitted patients described above, the authors have thus put forward some hypotheses that might explain these trends of decreasing mortality rates over time.

One of them is the extremely high hospital census and rapid implementation of new measures (i.e. isolation and personal protection procedures) especially in locations with very high rates of COVID-19 in March and April. This is consistent with the observation of the most rapid declines in mortality rates between the months of March – April and May – June, when health care workers gradually became more familiar with new procedures.

Changes in treatment protocols may also have contributed to this decreased mortality. The observed increased use of supplemental oxygen and decreased use of mechanical ventilation in the registry data could be explained by trends in respiratory care that emerged as the pandemic progressed, particularly the efficacious modalities of noninvasive ventilation, high flow nasal oxygen, and prone positioning, although these modalities were not captured in the registry. Substantially increased use of steroids and remdesivir may also have contributed to better outcomes.

Few limitations exist: the analysis was retrospective, with varying sample sizes due to the voluntary nature of enrolment in the registry. Certain treatment modalities were not captured. There was potential for bias due to confounding from unobserved or unrecorded characteristics in the estimation of associations, and as such causality cannot be inferred. Furthermore, it is important to note that this analysis included data from before the rollout of vaccines, and it would be interesting to see these more contemporary trends from the AHA COVID-19 CVD registry in future analyses.

Needless to say, such registry-based analyses provide important data on trends in mortality and contemporary management practices in the face of rapidly evolving hospital dynamics during the pandemic. While randomized controlled trials are essential to investigate potential treatments and inform evidence-based practice, the utility of such registries in identifying mortality and treatment trends in real-world practice, and indeed using this information to implement best practices, cannot be understated.

References

Alger HM, Rutan C, Williams JH IV, et al. American Heart Association COVID-19 CVD Registry powered by Get With The Guidelines. Circ Cardiovasc Qual Outcomes. 2020;13(8):e006967.
Roth GA, Emmons-Bell S, Alger HM, et al. Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic. JAMA Netw Open. 2021;4(5):e218828.
US Food and Drug Administration. Emergency Use Authorization (EUA) for emergency use of Veklury® (remdesivir) for the treatment of hospitalized patients with severe 2019 coronavirus disease (COVID-19). Published October 22, 2020. Accessed June 4, 2021. https://www.fda.gov/media/137564/download

International Clinical Trials Day: A conversation with Prof Martin Landray

May 20, 2021May 14, 2021 Aaysha Cader, MD, MRCP

International Clinical Trials Day (ICTD) is commemorated worldwide on the 20^th of May, in recognition of day on which James Lind started, what is widely believed to be the first randomized clinical trial, in 1747.^1,2 In search of a treatment for Scurvy, he recruited 12 subjects aboard the HMS Salisbury of the British Royal Navy fleet for his “fair test”, assigning two men to each of six different daily treatments for a period of fourteen days.²

First launched in 2005, ICTD is also an opportunity to celebrate the achievements of clinical trialists and vitally, raise awareness of clinical trials and the need for randomized evidence.¹ There has never been a greater need for randomized evidence than right now. In view of this, I’m delighted to have spoken with Professor Martin Landray, co-chief investigator of the RECOVERY trial, Professor of Medicine & Epidemiology at the Nuffield Department of Population Health, and Deputy Director at the Big Data Institute, University of Oxford, UK. We spoke about the incredibly successful RECOVERY trial,³ adaptive platform trials and the Good Clinical Trials Collaborative.⁴

I’m very grateful to Prof Landray for his time and insights, and I hope you learn from this hugely educational vlog as much as I did.

References

International Clinical Trials Day (ICTD) [Internet]. ECRIN – European Clinical Research Infrastructure Network. Available from: https://ecrin.org/international-clinical-trials-day-ictd
Milne I. Who was James Lind, and what exactly did he achieve? [Internet]. The James Lind Library, 2015. Available from: https://www.jameslindlibrary.org/articles/who-was-james-lind-and-what-exactly-did-he-achieve/
Randomised Evaluation of COVID_19 Therapy (RECOVERY) Trial [Internet]. Randomised Evaluation of COVID_19 Therapy (RECOVERY) Trial. Available from; https://www.recoverytrial.net/
Good Clinical Trials Collaborative [Internet]. Good Clinical Trials Collaborative. Available from: https://wellcome.org/what-we-do/our-work/good-clinical-trials-collaborative

Ramadan, COVID-19 and the cardiac patient

April 16, 2021April 14, 2021 Aaysha Cader, MD, MRCP

With the dawn of the Islamic lunar month of Ramadan, many Muslims around the world begin observing an absolute fast from dawn to dusk, abstaining from food, drink, and oral medications. The fast naturally also entails a change in lifestyle, sleeping patterns, and adjustments of salt and fluid intake, all of which have implications for the cardiac patient. Furthermore, as they are generally known to be on multiple medications, depending on the number of hours of fasting, there might be a need for adjusting drugs, doses, and timings.

Cardiac patients span across a wide range of diseases and differ in terms of symptoms, acuity, and hemodynamic stability. As such, while it might be entirely appropriate for stable patients to observe the fast, with adjustments to lifestyle, others who are less so may need to be advised against fasting, particularly as the sick are exempted. There is a paucity of data on best practices for fasting among cardiac patients. This blog provides a brief summary of the available data, some general suggestions, and links to useful resources pertinent to patients with common cardiac conditions on fasting during Ramadan.

Stable Coronary artery disease: Few observational studies suggest that with good monitoring, fasting may be safe in patients with stable treated coronary artery disease (CAD), particularly with normal left ventricular ejection fraction (EF), provided they adhere to medications.^1-3

In fact, among stable patients with a previous history of cardiovascular disease (CVD), fasting during Ramadan has been shown to significantly improve 10-year Framingham cardiac risk score, as well as cardiovascular risk factors such as lipid profile, body mass index (BMI), and systolic blood pressure.⁴

Acute myocardial infarction (MI): Unlike stable CAD, however, in patients with a recent acute MI or immediate post-cardiac surgery, abstinence from fasting following the 6-week period of either of these events has been advised.⁵^,6

Heart failure (HF): A prospective observational study examining the effect of Ramadan fasting on patients with chronic HF and reduced ejection fraction (< 40%), noted that as many as 92% of the patients that fasted had no changes or improved symptoms, while symptoms worsened in a minority of patients (8%).⁷ Furthermore, those with worsening symptoms were significantly less likely to have adhered to fluid and salt restrictions, and heart failure medications (p<0.0001). This clearly underscores the need for ensuring compliance with appropriately timed medications, particularly diuretics, in order to prevent acute decompensation of HF.

The British Islamic Medical Association has a structured guideline of recommendations based on risk for fasting among patients with heart failure:⁶

HF with preserved ejection fraction (HFpEF), and HF with reduced EF (up to an LV EF 35%) are at low/moderate risk for fasting (i.e. decision not to fast at the discretion of medical opinion and patient’s ability).⁶
Severe, but not advanced, heart failure is at high risk for fasting and should be advised not to fast. This would include patients on Cardiac Resynchronization Therapy (CRT) .⁶
Patients with advanced heart failure (including those on Left Ventricular Assist Devices), decompensated HF requiring large doses of diuretics^5, and those with severe pulmonary hypertension, are deemed very high risk, and MUST be advised against fasting.⁶

Hypertension: Fasting during Ramadan is generally well-tolerated in patients with well-controlled essential hypertension on the continuation of previous drug treatment ⁵^,8, supported by ambulatory BP measurement (ABPM) data in observational studies.^9-10. However, patients with resistant hypertension should be advised not to fast until their blood pressure is reasonably controlled.⁵ The key to blood pressure maintenance during Ramadan lies in compliance with medications, and non-pharmacological measures such as a low-salt diet.¹¹. In those with fluctuating BP, home blood pressure monitoring with medication adjustment may be a feasible option.

Adjustment of medications: Cardiac medications are vital, and non-compliance has the potential to be life-threatening. Patients should be advised on adherence to medication, and efforts be made to ensure compliance, by adjusting dose and timings, or switching to a class of medication that might be a more compliant alternative.⁸ For drugs with two daily doses, it’s advisable to take them with as wide a gap as possible during non-fasting hours.⁸ In case a medication requires more than twice daily dosing, an adjustment that allows for better compliance may be preferred.

Antihypertensive drugs: For twice-daily medication, dose timings may need to be changed to coincide with the early morning meal (Suhoor) and the breaking-of-fast meal (Iftar).⁸A switch to a once-daily medication with long-acting preparations may be preferred.^8,11

Diuretics: Diuretics are particularly unpopular among patients who either stop or reduce its doses during Ramadan. Diuretics may also worsen fasting-associated dehydration (especially in hot weather), with non-compliance resulting in uncontrolled hypertension and decompensation of heart failure. If the indication is hypertension, switching to a suitable alternative is reasonable.⁶ However, strict compliance with diuretics must be advised among those with HF especially those with reduced EF. They may also be prescribed during the non-fasting period of the day (i.e. early evening), where there is minimal risk of associated dehydration.⁵ Alternatively, patients may consider taking it at dawn (suhoor) to prevent frequent micturition and disturbed night sleep.⁶

Anticoagulants: Compliance must be ensured for those requiring therapeutic anticoagulation, irrespective of indication, with patients being advised of the risks of stroke or systemic embolism in case of non-adherence.¹²^,13 Some older small-scale observational studies have reported that Ramadan fasting does not appear to adversely influence the efficacy or safety of warfarin.¹⁴^{, 15} However, more recent data suggest that Ramadan fasting does in fact influence the therapeutic effect of warfarin in terms of lowered time spent in therapeutic range (TTR) with a reduced proportion of patients achieving therapeutic PT-INR and consequent increased risk of poor anticoagulation control.^{16, 17} As such, closer monitoring or dosage adjustments are necessary for patients maintained at the higher end of INR target ranges.¹⁶ This should extend to the post-Ramadan period, particularly in the elderly as they are more prone to over-anticoagulation and consequently the risk of bleeding.^{17, 18} ).

There is no randomized evidence on dosing adjustments for Novel oral anticoagulants (NOACs) with fasting during Ramadan.¹² However, clinical practice suggests that drugs are taken once or twice daily, such as NOACs, do not require an adjustment.¹² . Among patients on twice-daily NOACs such as apixaban, a switch to once-daily rivaroxaban might be feasible.⁶ Those taking rivaroxaban should be asked to take the NOAC with food even during the month of Ramadan.¹²

Antiplatelet medications: Patients must be strictly advised to continue dual antiplatelet therapy (DAPT), especially in case of a recent MI or percutaneous coronary stent implantation, with clear information on the adverse outcomes of non-compliance such as acute stent thrombosis, MI, and even death.⁶ In terms of P2Y12 inhibitors, given pharmacokinetics of ticagrelor, if twice-daily dosing proves challenging, a switch to single-dose P2Y12 inhibitors such as clopidogrel or prasugrel (if appropriate), may be considered.⁶

Ramadan, COVID-19, and vaccine uptake: With the rollout of vaccines currently underway globally, there are concerns about vaccine hesitancy, based on whether the intramuscular injection invalidates the fast, any possible side-effects, and if indeed the fast may have to be broken.¹⁹ Scholars have clarified that vaccination does NOT invalidate the fast and such clarifications must be widely disseminated among both cardiac patients and the general public in order to maximize vaccine uptake.²⁰

The bottom line to good heart health during Ramadan remains in good communication and preemptive discussions. Although the current climate of the COVID-19 pandemic poses challenges to in-patient visits and physical examinations, virtual consultations must be leveraged to optimize cardiac care during the month of fasting. Some useful resources have been linked in the references. This blog is by no means exhaustive, and decisions regarding individual patients’ suitability for fasting and medication adjustments must be made following individualized discussions with their respective physicians, particularly as the duration of the fast varies in different geographical locations and as such, not all data derived from studies can be extrapolated generically.

References

Salim I, Al Suwaidi J, Ghadban W, et al. Impact of religious Ramadan fasting on cardiovascular disease: a systematic review of the literature. Curr Med Res Opin. 2013;29(4):343-54.
Al Suwaidi J, Zubaid M, Al-Mahmeed WA, et al. Impact of fasting in Ramadan in patients with cardiac disease. Saudi Med J. 2005;26(10):1579-83
Mousavi M, Mirkarimi S, Rahmani, Get al. Ramadan fast in patients with coronary artery disease. Iran Red Crescent Med J. 2014;16:e7887.
Nematy M, Alinezhad-Namaghi M, Rashed MM, et al. Effects of Ramadan fasting on cardiovascular risk factors: a prospective observational study. Nutr J. 2012;11:69.
Chamsi-Pasha H, Ahmed WH, Al-Shaibi KF. The cardiac patient during Ramadan and Hajj. J Saudi Heart Assoc. 2014;26(4):212-5.
Ramadan Rapid Review & Recommendations – British Islamic Medical Association. Available at: https://britishima.org/wp-content/uploads/2020/05/Ramadan-Rapid-Review-Recommendations-v1.2.pdf (Accessed on 10th April 2021)
Abazid RM, Khalaf HH, Sakr HI, et al. Effects of Ramadan fasting on the symptoms of chronic heart failure. Saudi Med J. 2018;39(4):395-400.
Aadil N, Houti IE, Moussamih S. Drug intake during Ramadan. BMJ. 2004;329(7469):778-82.
Perk G, Ghanem J, Aamar S, Ben-Ishay D, Bursztyn M. The effect of the fast of Ramadan on ambulatory blood pressure in treated hypertensives. J Hum Hypertens. 2001;15(10):723-5.
Habbal R, Azzouzi L, Adnan K, et al. Variations tensionnelles au cours du mois de Ramadan [Variations of blood pressure during the month of Ramadan]. Arch Mal Coeur Vaiss. 1998;91(8):995-8.
Chamsi-Pasha M, Chamsi-Pasha H. The cardiac patient in Ramadan. Avicenna J Med. 2016 ;6(2):33-8.
Hersi AS, Alhebaishi YS, Hamoui O, et al. Practical perspectives on the use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with nonvalvular atrial fibrillation: A view from the Middle East and North Africa. J Saudi Heart Assoc. 2018;30(2):122-139.
Batarfi A, Alenezi H, Alshehri A, et al. Patient-guided modifications of oral anticoagulant drug intake during Ramadan fasting: a multicenter cross-sectional study. J Thromb Thrombolysis. 2021;51(2):485-493.
Saour JN, Sieck J, Khan M, et al. Does Ramadan fasting complicate anticoagulation therapy?. Ann Saudi Med 1989; 9: 538– 40.
Chamsi‐Pasha H, Ahmed WH. The effect of fasting in Ramadan on patients with heart disease. Saudi Med J 2004; 25: 47– 51.
Lai Y, Cheen M, Lim S, et al. The effects of fasting in Muslim patients taking warfarin. J Thromb Haemost 2014; 12: 349– 54
Sridharan K, Al Banna R, Qader AM, et al. Does fasting during Ramadan influence the therapeutic effect of warfarin? J Clin Pharm Ther. 2021 Feb;46(1):86-92.
Awiwi MO, Yagli ZA, Elbir F, et al. The effects of Ramadan fasting on patients with prosthetic heart valve taking warfarin for anticoagulation. J Saudi Heart Assoc. 2017;29(1):1-6.
Ali SN, Hanif W, Patel K, Khunti K; South Asian Health Foundation, UK. Ramadan and COVID-19 vaccine hesitancy-a call for action. Lancet. 2021:S0140-6736(21)00779-0.
Sharifain H. COVID-19 vaccine does not invalid the fast during Ramadan: Abdul Rehman Al Sudais. Available at: https://www.haramainsharifain.com/2021/03/covid-19-vaccine-does-not-invalid-fast.html. (Accessed on: April 12 2021)

Effects of COVID-19 on Acute Ischaemic Stroke care: Comparative insights from Get With The Guidelines-Stroke registry

March 17, 2021March 17, 2021 Aaysha Cader, MD, MRCP

Much like acute myocardial infarctions, the optimal management of acute ischaemic stroke (AIS) is extremely time-sensitive. The foundation of favorable outcomes of AIS lies in the timely presentation and acute intervention by means of either intravenous thrombolysis and mechanical thrombectomy. Especially earlier on during the COVID-19 pandemic, there was a concern regarding a decline in non-COVID acute medical admissions, as well as hospital-based challenges to appropriate and timely delivery of acute stroke care.

A study led by Dr Pratyaksh Srivastava and colleagues, published in Stroke, uses data from the American Heart Association (AHA)’s Get With The Guidelines Stroke (GWTG-Stroke)® registry, to compare characteristics, treatment patterns, and in-hospital outcomes of 81,084 patients over two time periods: before COVID and after the first reported case of COVID-19 (1). The AHA’s GWTG-Stroke registry is a validated and reliable national registry of adults with stroke in the United States (2,3). This blog provides a brief summary of the key findings of this analysis.

The study cohort and comparisons:

81,084 AIS patients were included over a period extending from 01^st November 2019 to 29^th June 2020, from among 458 participating hospitals with at least one positive COVID-19 patient. They were divided into two groups, according to the first reported case of COVID-19 in the registry. The pre-COVID group consisting of 39,113 patients (01^st November 2019 to 3^rd February 2020) and the during COVID group, consisting of 41,971 patients (4^th February 2020 to 29^th June 2020).

The two groups were compared for characteristics, treatment patterns, and outcomes. These analyses were repeated in sensitivity analyses, comparing a later during COVID-19 time period (1^st April 2020 to 29^th June 2020) to the same pre-COVID-19 time period. There were no differences in general characteristics among patients of the two time periods. 48.8% of the cohort were women. 61.9% were White. 2.7% of patients in the during COVID-19 group had a diagnosis of COVID-19.

Key findings from the study & implications:

There was a 15.3% average reduction of stroke presentations per week in the during-COVID-time period (3rd February 2020 to 24^th May 2020) when compared with similar months in 2019. This is perhaps a reflection of general trends (4,5) in the immediate aftermath of the pandemic, partially reflecting an anticipated lack of capacity in overburdened health systems, the effect of shelters in place and social distancing disorders (5), and patients delaying or avoiding seeking medical care due to concerns of contracting COVID-19(6).

Treatment patterns:

Similar rates of acute interventions for AIS were observed in pre-COVID and during-COVID time periods. There were no differences in rates of intravenous alteplase (11.7% vs. 11.4%, p=0.26) or endovascular therapy (10.2% vs. 10.1%, p=0.90) pre- and during COVID respectively.

Furthermore, there were also no additional delays in administering care. Median door to needle times (46 [32-65] minutes vs 46 [33-64] minutes; p= 0.69) and door to endovascular times (86 [53-129] minutes vs 90 [54-134] minutes; p=0.06) were not different between the pre-COVID and during COVID periods respectively. This is crucial and encouraging data, given the time-sensitive nature of acute stroke care and the delays that were anticipated during the COVID-19 period, from having to don personal protective equipment (PPE).

Also, door to computed tomography (CT) time was slightly shorter during the COVID-19 time period (median 35 [14-100] vs 37 [15-111] mins, p<0.001). A significant uptake of telestroke consult was observed during the COVID-19 period as compared with pre-COVID (6.0% vs 7.1%; p <0.0001).

GWTG-Stroke quality measures:

Slight decreases were observed in rates of timely IV alteplase administration, prescription of antithrombotics at discharge, dysphagia screen, smoking cessation counseling, stroke education, and rehabilitation consideration in the during-COVID-19 group. Despite this, these quality measures remained above the 85% target, suggesting the maintenance of quality care during the pandemic.

Outcomes:

Adjusted inpatient mortality of AIS was similar between pre- and during COVID-19 periods (4.8% vs. 5.2%; odd ratio 1.05, 95% CI 0.97-1.13), consistent with prior published studies (5,7). Also, in these adjusted models, no significant differences were observed for other outcomes such as symptomatic intracranial hemorrhage among IV alteplase patients, venous thromboembolism or pulmonary embolism during hospitalization.

In terms of patients’ disposition, there were reduced odds of discharge to skilled nursing facility (OR 0.78, 95% CI 0.74-0.82) and of a hospital stay >4 days during COVID-19 time period (OR 0.84, 95% CI 0.81-0.87), and increased odds of discharge to hospice (1.12, 95% CI 1.03- 1.21), and to home (OR 1.12, 95% CI 1.09-1.16) during COVID-19 period. These possibly reflect a hesitancy towards prolonged hospital stays, competing pressures on beds and skilled facilities, and tendency to triage away from high-risk environments.

Sensitivity analyses:

Apart from a slightly longer, and perhaps clinically insignificant, time from door to endovascular treatment in the later during COVID-19 group, findings remained largely similar in sensitivity analyses comparing those presenting in the later COVID-19 time period to those presenting pre-COVID-19.

Limitations:

Given its retrospective, observational nature, this study is limited in its ability to only evaluate, but not infer causality, with descriptive statistics performed being hypothesis generating. Not all data were complete and the observed decline in AIS patients during the pandemic may be due to lags in data entry. Furthermore, these findings may not be generalizable to hospitals that differ from GWTG-Stroke and international cohorts.

Key take-home message:

Despite an observed 15.3 % average decline in AIS presentations during the pandemic, this analysis from the GWTG-Stroke registry demonstrates preserved AIS care quality in the pre- and during COVID-19 time periods with similar door to needle, and door to endovascular times, similar rates of IV alteplase therapy, endovascular therapy, and adjusted in-hospital mortality.

For more latest science on Stroke and Neurology, be sure to register and attend the International Stroke Conference – happening now!

References

Srivastava PK, Zhang S, Xian Y, et al. Acute Ischemic Stroke in Patients With COVID-19: An Analysis From Get With The Guidelines–Stroke. Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034301
Ormseth CH, Sheth KN, Saver JL, Fonarow GC and Schwamm LH. The American Heart Association’s Get With the Guidelines (GWTG)-Stroke development and impact on stroke care. Stroke Vasc Neurol. 2017;2:94-105
Xian Y, Fonarow GC, Reeves MJ, Webb LE, Blevins J, Demyanenko VS, et al. Data quality in the American Heart Association Get With The Guidelines-Stroke (GWTG-Stroke): results from a national data validation audit. Am Heart J. 2012;163:392-8, 398 e1.
Diegoli H, Magalhaes PSC, Martins SCO, Moro CHC, Franca PHC, Safanelli J, Nagel V, Venancio VG, Liberato RB and Longo AL. Decrease in Hospital Admissions for Transient Ischemic Attack, Mild, and Moderate Stroke During the COVID-19 Era. Stroke. 2020;51:2315-2321.
Nguyen-Huynh MN, Tang XN, Vinson DR, Flint AC, Alexander JG, Meighan M, Burnett M,Sidney S and Klingman JG. Acute Stroke Presentation, Care, and Outcomes in Community Hospitals in Northern California During the COVID-19 Pandemic. Stroke. 2020;51:2918-2924
American College of Emergency Physicians. Public Poll: Emergency Care Concerns Amidst COVID-19 https://wwwemergencyphysiciansorg/article/covid19/public-poll-emergency care-concerns-amidst-covid-19. 2020.
Tejada Meza H, Lambea Gil Á, Sancho Saldaña A, Martínez-Zabaleta M, Garmendia Lopetegui E, López-Cancio Martínez E, et al; NORDICTUS Investigators. Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain. Eur J Neurol. 2020;27(12):2491-2498.

Reflections of 2020: adaptations and lessons learned

January 23, 2021January 22, 2021 Aaysha Cader, MD, MRCP

2020 came, a pandemic hit, and 2020 left. It was an extraordinary year in which words such as unprecedented, exponential and social distancing forced their way into our ordinary vocabulary. Hopefully, we won’t have to live another year like that in our lifetimes, but let’s exercise some cautious optimism in that respect. It took a toll on everyone, both physically and mentally, but perhaps the brunt of it was borne by essential workers, notably those involved in healthcare. Many had to work extra hours, often at the expense of time spent with loved ones, often young children. Many of us have not been able to visit family in almost a year, due to travel restrictions or for fear of transmitting the virus to elderly parents and relatives. Many have suffered setbacks in training and professional development. We are all tired – COVID fatigue is real. We all had it bad, in some way or the other, but in the face of adversity lies the opportunity: the pandemic forced us to adapt, and it looks like the lessons we learned last year are certainly applicable for the immediately foreseeable future.

COVID 19 served to magnify existing global healthcare disparities, triggering important conversations around it, and with that, hope for rectification. It saw the more widespread adoption of telemedicine as an integral component of healthcare delivery. It made the scientific community realize the importance of good quality research and clinical trials and the benefits of sharing knowledge and collaboration.

In pathology class at medical school, we are taught cellular responses to stress and toxic insults. Adaptations are one of them: Robbins pathology defines them as reversible functional and structural responses to more severe physiologic stresses and some pathologic stimuli, during which new but altered steady states are achieved, allowing the cell to survive and continue to function.¹

COVID-19 forced adaptations at a far greater magnitude, and we are now at the altered steady state of what we call a “new normal”. Just as much as the pandemic forced healthcare systems to adapt to the crisis, it presented an opportunity for introspection and re-evaluation of our lives on a personal level, and there are important lessons I’ve learned in the process.

Communication: Just as with telemedicine, 2020 also saw us embrace social media in a way we hadn’t before. Indeed, in an increasingly digital global landscape, many of us had to depend on virtual interactions as being the primary and often the sole form of interaction. In addition to public social media handles, many physicians took to their private accounts to combat misinformation, providing an important channel for public health messaging among friends and social circles outside of medicine. With the advent of vaccines, this appears to be even more important in breaking down important information and allaying fears related to its side effects.

Adaptations in learning: Also virtually, we learnt to modify methods of learning, with conferences and meetings adapting to virtual platforms and regular educational content being far more widely available. Paradoxically, this has perhaps resulted in increased exposure and visibility of especially early career physicians, with opportunities for global networking and collaborations. Not too different from the times of in-person conferences, we now look forward to “meeting” friends on webinar platforms, with the camaraderie and friendly exchanges with colleagues in healthcare probably being more therapeutic than the educational content itself.

Building a support network: Perhaps my greatest learning from the last year is the importance of friendship, support, and mentorship. While we’ve been trained to adapt and be strong, this is a pandemic none of us have been equipped for. We’re used to being care-givers, not receivers, but in remembering that we’re also human and vulnerable, it is only healthy to actively seek out and lean on one’s support network: this can be family, friends, sometimes colleagues: to talk, chat, cry it out, or rant.

Mentorship: We have all faced challenges that were unprecedented and it was more than just training that was affected. Navigating through the uncertainties of early career practice can be challenging even in the most ordinary of times; hence the perspectives, solid life advice, and clarity provided by good mentorship during pandemic times cannot be understated. Additionally, the stress of working in a pandemic can give rise to inopportune moments, and I couldn’t be more grateful for mentors that have cut me slack, forgiven the shortcomings, and taught me resilience. It’s a lesson in maturity that I hope I can pay forward in my dealings with junior physicians as well.

Gratitude: Count your blessings and force yourself to do this. Pause to celebrate the small victories.

As far as the science of adaptations goes, Robbins pathology will also tell you that when the stress is eliminated, the cell can recover to its original state without having suffered any harmful consequences.¹ While it looks like we’re in for a few more challenging months before the “stressful” triggers might show any signs of waning, my optimistic takeaway is precisely the hope of this recovery to its original state, or at the very least, some semblance of a better new normal.

2020 is the year that taught me resilience, and it is a testament to our ability to adapt and pivot. I’m sure we’ve all found different mechanisms of adaptations that work for each of us, and I’d love to hear yours!

References

Kumar v, Abbas AK, Aster JC. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death. In Robbins & Cotran Pathologic Basis of Disease. 10th ed. New York, NY: Elsevier; 2020.

From evidence to practice: Insights from the GWTG-HF Registry on the Applicability of FDA Labeling for Dapagliflozin in Heart Failure with Reduced Ejection Fraction

December 16, 2020December 15, 2020 Aaysha Cader, MD, MRCP

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors continue to amaze the world of cardiovascular pharmacotherapeutics. Initially developed as anti-diabetic agents, SGLT-2 inhibitors have demonstrated a wide range of benefits across various patient subsets, most notably those with heart failure.

The landmark Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, a phase 3, placebo-controlled trial the results of which were published in November 2019, demonstrated that the SGLT-2 inhibitor dapagliflozin reduced mortality and worsening heart failure events, and improved health-related quality of life among patients with heart failure with reduced ejection fraction (HFrEF), regardless of the presence or absence of diabetes.¹

Based on these DAPA-HF trial results, in May 2020, dapagliflozin was the first SGLT-2 inhibitor approved by the US Food and Drug Administration (FDA) for HFrEF.² However, as previous registries have shown, many novel evidence-based therapies are either delayed or not optimally utilized in practice. ^3,4 Thus, in order to determine the proportion of eligible candidates for the initiation of dapagliflozin and define potential barriers to therapeutic optimization, an analysis of the American Heart Association (AHA)’s The Get With The Guidelines®–Heart Failure (GWTG-HF) registry was undertaken by Vaduganathan and colleagues. This blog is a summary of the results of this analysis, part of TRANSLATE-HF research platform, the results of which were presented at AHA Scientific Sessions 2020, with simultaneous publication in JAMA Cardiology.⁵

The GWTG-HF registry: This a large contemporary hospital-based quality improvement registry including a total of 586,580 patients from 529 sites across the United States.

Population of interest: After exclusion criteria were applied, the primary study cohort for this analysis included 154,714 patients hospitalized with HFrEF at 406 sites between January 2014 – September 2019. As with DAPA-HF, the focus was on chronic HFrEF (≤40%) and treatment eligibility of patients based on discharge parameters during the transition to ambulatory care.

Treatment candidates for Dapagligflozin: The FDA label excluded patients with type 1 diabetes and chronic kidney disease (i.e. estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m² and dialysis). When this FDA label was applied to patients in the above cohort, 81.1% would be candidates for dapagliflozin, with similar proportions across all study years (range 80.4-81.7%). When analyzed for 355 sites with ≥10 hospitalizations (enrolling 154,522 patients), the median proportion of FDA label candidates was similar, at 81.1%.

Eligibility according to diabetic status: Notably, the proportion of eligible patients for dapagliflozin was higher among those withOUT a history of or new diagnosis of diabetes, as compared with those with type 2 diabetes (85.5% vs. 75.6%).

Reasons for not meeting FDA label: The predominant reason for ineligibility for dapagliflozin in this cohort was an eGFR<30 mL/min/1.73 m² at discharge; this was more frequent among diabetics (23.9%) than non-diabetics (14.3%). Other reasons were far less frequent: 3.2% were ineligible due to chronic dialysis and only 0.02% due to type 1 diabetes.

Especially in terms of ineligibility for Dapagliflozin reported in this publication, it is important to note that this data analysis was undertaken between April 1^st to June 30^th, 2020. More compelling data from two other pivotal SGLT-2 trials reported after DAPA-HF are likely to further extend SGLT-2 inhibitor treatment indications to patients with more severe CKD. DAPA CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease⁶ evaluated patients with albuminuric chronic kidney disease with eGFR down to as low as 25mL/min/1.73 m²and EMPEROR-Reduced⁷ evaluated patients with HFrEF with eGFR as low as 20mL/min/1.73 m^2.

Differences between DAPA-HF Trial Participants vs. FDA Label Candidates in GWTG-HF: Participants in DAPA-HF were younger, less often women, and less often Black compared with participants in GWTG-HF, underscoring the need for greater representation of older adults, women, racial/ethnic minority groups, and those with multiple comorbidities in clinical trials relative to reference usual care (i.e. registry) populations. GWTG-HF registry participants had lower left ventricular EF and eGFR; however, a history of myocardial infarction and percutaneous coronary intervention) were more prevalent among DAPA-HF participants. The overall prevalence of diabetes was similar between both cohorts (44.1% in GWTG-HF registry vs 45% in DAPA-HF population). There was a lower use of evidence-based HF medical therapies among GWTG-HF participants, but higher use of implantable-cardioverter defibrillators. Most other clinical characteristics were qualitatively similar between the two groups

Conclusions & implications: A lag from clinical trial to clinical practice is not uncommon for most novel pharmacotherapeutics. However, data from this large, contemporary US hospitalized HF registry show that 4 out of 5 patients with HFrEF, irrespective of type 2 diabetes status are candidates for initiation of dapagliflozin at hospital discharge, supporting broad generalizability to practice. This represents a potential opportunity for in-hospital implementation of evidence-based medical therapies and treatment optimization of stable chronic HFrEF, pending data on safety and efficacy of SGLT2 inhibitors in acute HF (NCT04363697, NCT04298229, NCT04157751).

References

McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
US Food and Drug Administration. FDA approves new treatment for a type of heart failure. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-type-heart-failure. Accessed on December 1, 2020.
Greene SJ, Fonarow GC, DeVore AD, et al. Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol. 2019;73(19):2365-83.
Greene SJ, Butler J, Albert NM, et al. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry. J Am Coll Cardiol. 2018;72(4):351-66.
Vaduganathan M, Greene SJ, Zhang S, et al. Applicability of US Food and Drug Administration Labeling for Dapagliflozin to Patients With Heart Failure With Reduced Ejection Fraction in US Clinical Practice: The Get With the Guidelines-Heart Failure (GWTG-HF) Registry. JAMA Cardiol. 2020 Nov 13:e205864. doi: 10.1001/jamacardio.2020.5864
Heerspink HJL, Stefánsson BV, Correa-Rotter R. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24. PMID: 32970396.
Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413-24. 32865377.

#AHA20 and#COVID-19: Late-breaking science insights from the AHA COVID-19 registry

November 20, 2020November 20, 2020 Aaysha Cader, MD, MRCP

The American Heart Association (AHA) COVID-19 registry, leveraging the existing AHA Get With The Guideline (GWTG) platform, was developed to better understand hospital outcomes and adverse cardiovascular complications for patients with COVID-19.

The registry was formulated to accelerate the pace of COVID-19 research and quality improvement, where granular data were collected and analyzed at an unprecedented pace, shortening time to discovery and dissemination of results. As of November 9, 109 sites across the United States had enrolled over 22,500 patients in the registry. Data derived from the registry provided for some interesting results, presented at the late-breaking science session 7 at AHA Scientific Sessions.

Cardiovascular risk factors: The vast majority of hospitalized COVID-19 patients had cardiovascular risk factors, with only fewer than 15% having no traditional risk factors. Hypertension predominated (~60%), followed by diabetes (35%) and notably, obesity (45%).

In-hospital cardiac complications: The registry predominantly found that in-hospital cardiac complications occurred less frequently than initially feared, with the cardiovascular (CV) composite of complications (including CV death, myocardial infarction [MI], stroke, heart failure and shock) occurring in approximately 8.8%. Individual CV complications occurred as follows: MI ~3%; stroke, heart failure, and shock ~2%. Myocarditis was uncommon, occurring in 0.3%. Deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 3.8%, substantially lower than those reported in prior single center reports.

The death occurred in ~19.5% in total, with respiratory causes predominating (72%) and only 10% being attributed to a cardiac cause. 18% had other causes, commonly sepsis. The need for mechanical ventilation was ~20%.

Racial and Ethnic Differences in Presentation and Outcomes for Patients Hospitalized with COVID-19 [1]

Race and ethnicity data of 7,868 hospitalized patients across 88 registry sites from Jan 1 to July 22, 2020 revealed an over-representation of Black and Hispanic patients, who accounted for >50% of hospitalizations. They were significantly younger than patients of other ethnicities at the time of hospitalization. Hispanics were more likely to be uninsured.

The longest duration from symptom onset to hospital arrival and a diagnosis of COVID was observed in Asian patients, who also had the highest cardiorespiratory disease severity at presentation.

There was a significant burden of CV risk factors among black patients with obesity (49.3%), diabetes (45.2%), and hypertension (69.9%) being the highest reported prevalence across ethnic groups.

Mortality: The overall mortality in this dataset was 18.4% with a total of 1,447 deaths, among which, 53% occurred among Hispanic and Black patients. However, after adjusting for sociodemographic, clinical, and presentation features, mortality and major adverse cardiovascular or cerebrovascular events did not differ by race/ethnicity.

Nevertheless, given the greater burden of mortality and morbidity of Black and Hispanic patients, the authors recommended that interventions to reduce disparities in COVID-19 be focused upstream from hospitalizations.

Association of Body Mass Index (BMI) with Death, Mechanical Ventilation, and Cardiovascular Outcomes in COVID-19 [2]

In an important analysis looking at the association of BMI with COVID-19 outcomes, this study found that obesity, and particularly class III obesity, is over-represented in the registry among patients of COVID19, with the largest differences observed among adults < 50 years. Higher obesity class associated with younger age. Higher BMI class was also associated with a higher prevalence of the black race.

Among 7606 patients, the composite primary endpoint of in-hospital death or mechanical ventilation occurred in 2109 (27.7%) patients. After multivariable adjustment, classes I to III obesity were associated with progressively higher risks of in-hospital death or mechanical ventilation. Significant BMI by age interactions was seen for all primary endpoints. There was no association between obesity class and major adverse cardiac events (MACE). As for venous thromboembolism, Class II obesity was associated with a composite higher risk of venous thromboembolism.

Severe obesity (BMI ≥40 kg/m2) was associated with an increased risk of in-hospital death only in those ≤50 years (hazard ratio, 1.36 [1.01–1.84]). In light of these findings, the authors underscored the importance of clear public health messaging and a rigorous adherence to COVID-19 prevention strategies in all obese individuals regardless of age, but especially those <50 years who may underestimate their risk for COVID-19.

The entire session can be viewed on-demand until the 4^th of January 2020: AHA Goes Viral: COVID-19, Influenza Vaccines, and Cardiovascular Disease. Both the above studies were also simultaneously published in Circulation.

References:

Rodriguez F, Solomon N, de Lemos JA, Das SR, Morrow DA, Bradley Smet al. Racial and Ethnic Differences in Presentation and Outcomes for Patients Hospitalized with COVID-19: Findings from the American Heart Association’s COVID-19 Cardiovascular Disease Registry. Circulation. 2020 Nov 17. doi: 10.1161/CIRCULATIONAHA.120.052278. Epub ahead of print.
Hendren NS, de Lemos JA, Ayers C, Das SR, Rao A, Carter S. Association of Body Mass Index and Age With Morbidity and Mortality in Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry. Circulation. 2020 Nov 17. doi: 10.1161/CIRCULATIONAHA.120.051936. Epub ahead of print.

#AHA20: Be in the ‘Zoom’ Where It Happens

November 14, 2020November 17, 2020 Aaysha Cader, MD, MRCP

Last year, I blogged about my experience of attending AHA Scientific Sessions for the first time as an international attendee. As I reminisce about the wonderful experiences and front row seats to the Hamilton musical performance (The Room Where It Happens) at the opening session of #AHA19, I am equally amazed at the fabulous scientific content and networking opportunities available with this year’s #AHA20 virtual format.

Late-breaking science (LBS)

Late-breaking science sessions are always one of the highlights of scientific sessions that I really look forward to. #AHA20 has nine late-breaking sessions spanning across various sub-specialties of cardiology on all 5 days of scientific sessions. With questions being posed to presenters by the social media moderators in real-time, every effort has been made to replicate the exciting component of late-breakers as much as possible, giving us the experience of “being in the room (or in this case zoom)” where it happens. The additional “Meet the trialists” segment offers further opportunities for interactive conversations with select researchers who will provide answers and insights to questions that very often occur in the immediate aftermath of late-breaking science.

The Heart Hub: Something for everyone

Scientific sessions have always had something for everyone, with the Heart Hub being the hub of activity. This year promises no less, with an easy-to-navigate platform taking you to the various dedicated “lounges”. #AHA20 also offers some incredible informal networking sessions, panel discussions, and programming targeted to specific communities (women in cardiology, early careers, and fellows-in-training #AHAFIT). #AHA20 is extra special for me, as I had the opportunity to be a part of an incredibly inspirational session on the Imposter Syndrome, with powerhouse women in cardiology sharing refreshingly honest takes on their experiences and advice on how they overcame it. Fellow #AHAEarlyCareerBlogger Kylia Williams shares some highlights here.

Social Media & Virtual Networking

Despite the “virtualness” of scientific meetings, almost a year into the pandemic, we have all rapidly adjusted to this new normal. As fellow #AHAEarlycareerBlogger Mo Al-Khalaf blogged, social media has been leveraged to increase virtual conference interactions and networking between peers. This has also, inadvertently perhaps, showcased the increasing need to build one’s professional social media brand. Here’s an on-demand session we put together on how to best build and protect one’s brand. Please do also join us for a live Q&A panel discussion today (Saturday, November 14^th, 6-7 pm CT) at the Go Red Women in Science and Medicine lounge Zoom Room B.

With four more science-packed days to go, I’m excited about everything else #AHA20 has to offer. I’ll be live-tweeting late-breakers and content on interventional cardiology throughout sessions. Make sure you follow the #AHA20 social media ambassadors for each day on Twitter, as well as the virtual co-pilots to help navigate your conference experience and be in zoom where it happens.