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Haemostatics: Stephen Hales and the first direct measurement of blood pressure

Blood pressure lowering medications are among some of the most effective and useful medications currently used in medicine. In 2017 the ACC/AHA released new guidance for the evaluation and management of high blood pressure in adults.1 This guidance outlines what is considered normal, elevated, and hypertension in adults.1 We now understand the great importance of blood pressure in health but this wasn’t always the case.

As far as we know, blood pressure was first mentioned by G. Harveo (1628) where he warned surgeons that blood could “jet out” of the artery.2 What I was interested in was the first measurement of blood pressure as we know it. That first measurement was done by Reverend Stephen Hales in 1733.2

I remember learning this during undergrad, and the image is striking. It is a picture of Hales and his associate with a horse laying on its side. They inserted a brass tube into the femoral artery connected to a glass tube running vertically out of the horse’s neck.3 The blood reached 8 feet 3 inches.4 Further work by Hales and others went on to describe blood pressures in different species and different vascular beds, but I haven’t been able to get the image of this horse out of my head.2

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3(http://www.epi.umn.edu/cvdepi/wp-content/uploads/2011/05/Hales-Horse.jpg)

3(http://www.epi.umn.edu/cvdepi/wp-content/uploads/2011/05/Hales-Horse.jpg)

As my last post for the AHA Early Career Bloggers, I wanted to look into Stephen Hales. Who was he? Why did he do this experiment in the horse? And what else did he do? Hales was a Reverend in Middlesex who dabbled in many scientific pursuits. What I was interested in were those pertaining to the cardiovascular system. I went directly to the source: Statical Essays Containing Haemastatics.4

4 https://books.google.com/books?id=uDQ-AAAAcAAJ (eBook)

4 https://books.google.com/books?id=uDQ-AAAAcAAJ (eBook)

 

To get some context, this is what was thought about the cardiovascular system of arteries and veins at the time, “As an animal body consists not only of a wonderful texture of solid parts, but also of a large proportion of fluids, which are continually circulating and flowing, through and inimitable embroidery of blood vessels…it has, ever since the important discovery of the circulation of the blood, been looked upon as a matter well worth the inquiring into, to find the force and velocity with which these fluids are impelled…”4

This book doesn’t have any illustrations, unfortunately, but there are descriptions of the many experiments Hales performed. He repeated his experiment on pressures in the horse several times. In fact, the famous image of Hales with the horse was from his 3rd horse experiment. Eventually Hales started collecting the blood and determining how much there was in addition to pouring wax into the empty heart to make a cast and determine the chamber volumes. He compiled this into a pair of tables. 4

4 https://books.google.com/books?id=uDQ-AAAAcAAJ (eBook)

 

Based on Hales’ measures, he calculated that “a quantity [of blood] equal to the dog’s weight, will pass through the heart in 11.9 minutes”. You’ll notice that Hales made calculations for “Man” but these were derived from data from the other animals and he never performed these experiments on humans.4

Stephen Hales contributed to science in many ways including in other fields. He is famous for inventing a ventilator that circulated air in ships, prisons, and mines which likely saved many lives. Hales had no medical training. He obtained a bachelors degree in divinity and a Master of Arts. Hales is a reminder that great discoveries can be made by anyone with a curious mind.5

4 https://books.google.com/books?id=uDQ-AAAAcAAJ (eBook)

4 https://books.google.com/books?id=uDQ-AAAAcAAJ (eBook)

 

Don’t forget to register for #Hypertension19 happening this September 5-8 in New Orleans! 

 

References

  1. https://www.heart.org/-/media/data-import/downloadables/hypertension-guideline-highlights-flyer-ucm_497841.pdf
  2. The history of blood pressure measurement: from Hales to our days. V.A. Tsyrlin, M.G. Pliss, N.V. Kuzmenko. April 2016. Arterial Hypertension.
  3. http://www.epi.umn.edu/cvdepi/wp-content/uploads/2011/05/Hales-Horse.jpg (http://www.epi.umn.edu/cvdepi/essay/reverend-stephen-hales-on-blood-pressure/)
  4. Stephen Hales. Statical Essays Containing Haemastatics. (eBook: https://books.google.com/books?id=uDQ-AAAAcAAJ
  5. https://en.wikipedia.org/wiki/Stephen_Hales

 

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Big data, machine learning & artificial intelligence — how BCVS19 showed me that basic cardiac researchers needs to take these more seriously.

I had one main goal this year when I attended BCVS19 in Boston: go to sessions I normally wouldn’t.

Basic cardiac researchers, myself included, can sometimes have a very narrow field view. We tend to focus on the workhorse of the heart, the cardiac myocytes. For a long time, other cell types were completely overlooked. Only recently have big conferences, like BCVS19, started to have more sessions focused on the unsung heart heroes like fibroblasts, inflammatory cells and even fat. These are now the norm now, which is definitely how it should be.

At BCVS19 this year, sessions such as “Beyond Myocytes and Fibroblasts: Forgotten Cells of the Heart” and “The Future of Cardiac Fibrosis” provided myocyte-free perspectives that are desperately needed. While I was excited to experience these talks, I noticed there’s another area that is critical to the future of cardiac research that I’ve been overlooking.

The last couple sessions touched on how to handle big data, machine learning and artificial intelligence (AI) both in basic research and clinical settings.

Based on session attendance, I wasn’t the only one who had been overlooking these topics.

Now, this low turnout could be because these sessions were towards the end of the conference, but I’m not sure that’s actually the case. Either way, I’m glad I decided to make it because I found myself wanting to know more about pretty much everything that was discussed, which is basically the whole point of going to conferences, right?

TheAdvances in Cardiovascular Research — New Techniques Workshop” was a panel of experts fielding questions from the audience. I was most struck by the information Dr. Megan Puckelwartz from Northwestern provided about her experience doing human whole genome sequencing experiments. Among many things, Dr. Puckelwartz mentioned that universities need to prepare themselves for the future of genomic research because most institutions don’t have the storage capacity needed for this analysis. The scale of data storage needed is massive, but few institutions are ready. Advances in genomic research are fast approaching personalized medicine becoming a reality, but we can’t harness the power of these experiments if we don’t have anywhere to store the data.

More people should be talking about this and discussing concrete solutions.

On the last day of the conference, on a whim I decided to attend the “Machine Learning, Big Data and AI in Heart Disease” session, which was worth it.

Simplified model of how machine learning works. Source: https://machinelearning-blog.com/2017/11/19/fsgdhfju/

Simplified model of how machine learning works. Source: https://machinelearning-blog.com/2017/11/19/fsgdhfju/

Kelly Myers, the chief technology officer from the Familial Hypertension (FH) Foundation talked about their work focused on creating an algorithm to better diagnose FH patients from their national registry/database called CASCADE. This was desperately needed because even though 1 in 250 people have FH, only ~15% of patients with FH have been identified, mostly because current biomarkers aren’t sensitive enough. With their machine learning algorithm and collaborating with several institutions and physicians, they’ve been able to identify 75 factors that fit into six distinct categories that are predictive of the disease. Looking at lab results alone isn’t enough — more information is needed but this wouldn’t have been understood without a machine learning approach.

Dr. Qing Zeng, the Director of the Biomedical Informatics Center at GW School of Medicine also talked about her AI/ deep learning approaches focused on improving the cardiac field. She mentioned that using deep learning approaches is advantageous due to their ability to model highly non-linear relationships. She also discussed that the main challenge in applying this approach to clinical data is that it’s not a magic pill — clinical data is highly complex. There are many missing values and researchers have to present the data in a way physicians will accept/understand. Because Dr. Zeng’s work was focused on creating a model that could predict if heart surgery was worth it for patients who were deemed “frail”, the cooperation from the cardiac surgeons is key.

When asked “Have you asked surgeons if your score aligns with their opinion about whether a patient should have surgery?” Dr. Zeng responded: “This is tough, we would like to compare what we recommend against what humans expect, but cardiac surgeons aren’t willing to give us a score, so we have a hard time pinning down it actually means to evaluate this against humans.” To make AI/deep learning studies relevant, the researchers and physicians need to figure out how to communicate.

Overall, I learned a lot from these sessions because they highlighted how far the field needs to grow in these areas. Looking forward to BCVS20 next year to see if we’ve figured out a way to work through these growing pains.

 

 

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Bifurcations: EPISODE 3 – TAP TECHNIQUE

As the summer holidays wind down to the final few days, many of us are heading back to the routine of work, school and home.  With the end of summer, my Bifurcation Series comes to a close as well. The final episode is the TAP technique.

Operators find this to be the least cumbersome of all the 2-stent strategies. Many resort to it during emergencies as the access to the main branch (MB) is maintained throughout the procedure. The steps are fewer which ensures expeditious coverage of both vessels followed by the conventional optimization steps including kissing and proximal optimization with a non-compliant balloon. Similar to culotte, this strategy allows operators to start with a provisional strategy and convert to TAP should the need arise. In addition, there is minimal stent overlap. This technique is considered a modification of what was formally known as T-stenting. The primary limitation of the original T-stenting was missing the ostium of the side branch (SB). This geographic miss is what prompted many operators to perform minimal protrusion to mitigate in-stent restenosis at that missed segment. Hence the name TAP, T and small protrusion, was coined. Although this technique has been adopted worldwide, there are no large randomized trials with long term outcome data to reference. There are some published data; however, that are worth reviewing.

 

Study TAP strategy Patients (n) Unprotected
left main stem
Follow-up
duration
TVR Definite stent
thrombosis
Burzotta et al’ Bail-out TAP in provisional 73 37.0% 9 months 6.8% 1.40%
Al Rashdan
et al7
Systematic TAP 156 10.3  % 36 months
(range 24-48 months)
5.3% 0.06%
Burzotta et a1 Bail-out TAP in
provisional procedures
19 5.0% 12 months 5.3% none
Naganuma et al Bail-out TAP (type B dissection or
TlMI <3 or stenosis >50% in the SB)
95 18.9% 36 months 9.7% none
ARTEMIS
study10
Bail-out TAP (type B dissection or
TlMI <3 or stenosis >75% in the SB)
71 26.8% 12 months 8.5% none
 SB:side branch;TVR: target vessel revascularisation

 

Burzotta et al, 2007

The modification of the T-stenting was first described in 2007 by Burzotta et al.1 It was evaluated in vitro and in two independent series of patients undergoing elective drug-eluting stent (DES) implantation on a bifurcation lesion. In vitro testing demonstrated perfect coverage of the bifurcation with minimal stent’s struts overlap at the proximal segment of SB ostium with a single layer stent struts. Sirolimus, paclitaxel, or zotarolimus DES were deployed in 73 patients (67% with Medina 1,1,1 lesions and 44% of unprotected distal left main disease) using the TAP technique. The procedural success was achieved in all cases. At 9 months the clinically-driven target vessel revascularization (TVR) was 6.8%. Since this was a pilot study, the investigators recommended larger outcome trials to further evaluate this technique. No comparison arm was available in this initial trial.

 

Al-Rashdan et al, 2009

In 2009 Al-Rashdan et al published their series of 156 consecutive patients who underwent TAP stenting.2 This was a single center study that resulted in a 99% procedural success rate and a major adverse cardiac events (MACE) free survival rate of 88% at 36 months average follow up. The TVR rate was 5.3%. Although to date this represents the largest cohort of TAP cases, the results are limited to a single center with no randomization which precludes further conclusions.

 

Burzotta et al, 2009

In 2009, Burzotta’s group prospectively enrolled 266 consecutive patients requiring treatment of a bifurcation lesion.3 The MB was treated with a DES and TAP was reserved as a bailout strategy. Only 19 of the total required a bailout 2-stent strategy. Nine percent of the total had unprotected left main disease. At one year, the MACE rate was 8.2%. A non-hierarchical analysis revealed a 0.4% cardiac death, 4.1% MI, 4.5% TVR and 2 of the total had probable stent thrombosis (ST).  Given the small number of bailout 2-stent strategy arm, this study only demonstrates safety.

 

Naganuma et al, 2013

Naganuma et al retrospectively analyzed data of all patients who underwent TAP technique with DES between July 2005 and January 2012.4 A total of 95 patients were enrolled. Angiographic procedural success was achieved in all cases. A true bifurcation was found in 78.9% of those enrolled. The 3-year MACE, cardiac death or myocardial infarction, TVR and target lesion revascularization (TLR) rates were 12.9%, 3.1%, 9.7%, and 5.1%, respectively. No ST was observed in this cohort. Once again, the investigators recommend larger trials to make solid recommendations.

Naganuma et al, JACC Cardiovasc Interv. 2013;6:554-61.

Naganuma et al, JACC Cardiovasc Interv. 2013;6:554-61.

 

ARTEMIS Study 2014

The ARTEMIS study was published in 2014.5 It evaluated the mid-term angiographic results of TAP as the bailout strategy in symptomatic patients who were treated with one-stent strategy (DES of the MB) and kissing balloon inflation of the SB who subsequently developed impingement of the branch. TAP was performed if residual diameter stenosis of SB was ≥75%, presence of ≥type B dissection or flow impairment of the SB occurred. A total of 71 patients were enrolled with a MEDINA classification 1,1,1 lesions occurring in 60% of the total. At 9 months, restenosis was occurred in 12.5% of the total. Late lumen loss in the MB and SB was 0.22 ± 0.19 and 0.34 ± 0.37 mm, respectively.

 

Dzavik et al, 2014

In 2014, there was much hype revolving around bioresorbable technology. Dzavik et al performed in vitro bifurcation stenting employing different modalities on synthetic arterial models.6 The everolimus-eluting bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, California) (BVS) was used. A low-pressure final kissing balloon inflation was performed to complete the procedures. The results demonstrated that a single-stent technique optimally opened the SB without deforming the BVS in the MB. T or TAP-stenting covered the SB ostium completely. Culotte and crush with 2 BVS stents was successful; however, disruption was reported after the low pressure kissing inflation in one case. Investigators concluded that it was feasible to perform bifurcation stenting with BVS in large caliber vessels. They also recommended that a provisional strategy as the default. TAP or T-stenting with a metal DES is preferable. As the overall in vivo outcome data for BVS remains cautionary at best, the use of BVS outside clinical trials is not recommended whether for focal type A lesions or complex bifurcations.

The technique itself is illustrated below. As mentioned earlier, it is one of the simpler 2-stent strategies. Like other strategies, appropriate sizing, positioning and optimization ultimately dictate the final angiographic and clinical outcomes. Intracoronary imaging facilitates these crucial steps. Yet, as with all interventions, judgment is the cornerstone of any successful procedure. When appropriate, and based on both Syntax score and clinical scores, surgical revascularization should be considered. When one opts for percutaneous revascularization, the indication for the procedure, its potential risks and complexity should be shared with the patient. For operators, judging the significance of the SB, the angle of the bifurcation, the size of both vessels and the need for mechanical circulatory support is valuable. Finally, complex bifurcation stenting is not for everyone. When appropriate, such complex procedures should be referred to expert operators for the best outcomes.

Animations/illustrations courtesy of Graphic Designer Dania Al-Shaibi

Email: dn.alshaibi@gmail.com

 

 

References:

  1. Burzotta F, Gwon HC, Hahn JY, Romagnoli E, Choi JH, Trani C, Colombo A. Modified T-stenting with intentional protrusion of the side-branch stent within the main vessel stent to ensure ostial coverage and facilitate final kissing balloon: the T-stenting and small protrusion technique (TAP-stenting). Report of bench testing and first clinical Italian-Korean two-centre experience. Catheter Cardiovasc Interv.2007;70:75-82.
  2. Al Rashdan I, Amin H. Carina modification T stenting, a new bifurcation stenting technique: clinical and angiographic data from the first 156 consecutive patients. Catheter Cardiovasc Interv.2009;74:683-90.
  3. Burzotta F, Sgueglia GA, Trani C, Talarico GP, Coroleu SF, Giubilato S, Niccoli G, Giammarinaro M, Porto I, Leone AM, Mongiardo R, Mazzari MA, Schiavoni G, Crea F. Provisional TAP-stenting strategy to treat bifurcated lesions with drug-eluting stents: one-year clinical results of a prospective registry. J Invasive Cardiol.2009;21:532-7.
  4. Naganuma T, Latib A, Basavarajaiah S, Chieffo A, Figini F, Carlino M, Montorfano M, Godino C, Ferrarello S, Hasegawa T, Kawaguchi M, Nakamura S, Colombo A. The long-term clinical outcome of T-stenting and small protrusion technique for coronary bifurcation lesions. JACC Cardiovasc Interv. 2013;6:554-61.
  5. Jim MH, Wu EB, Fung RC, Ng AK, Yiu KH, Siu CW, Ho HH. Angiographic result of T-stenting with small protrusion using drug-eluting stents in the management of ischemic side branch: the ARTEMIS study. Heart Vessels.2014 Mar 14.
  6. Dzavik V, Colombo A. The absorb bioresorbable vascular scaffold in coronary bifurcations: insights from bench testing. JACC Cardiovasc Interv.2014;7:81-8.

 

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Peer Review Vs ‘Poor’ Review – Can a Systematic Plan Ensure Quality?

I was feeling a little disgruntled after in spite of two rounds of reviews, a reputable journal turned down a recent research effort of mine. I couldn’t help but disagree with many of their reviewers’ comments (I believe is a common sentiment among authors)– especially when some of them appeared to be very superficial and abstract. However, having reviewed for quite a few of the prominent and “high impact” cardiology journals myself, it eventually made me pause and think if I had been guilty of the same on occasion in the past. That led me to look up best practices for peer reviewing a manuscript, specifically for a cardiology journal. However, I did not have any significant success on locating such “guidelines.”

Peer review is largely considered to be a noble responsibility of a researcher, and considered an imperative skill for junior investigators.  I tried to come up with some semblance of a protocol for myself to save time in future peer review endeavors.

First and foremost, comes the decision to actually accept the peer review. In this day of mushrooming journals and inconsistent quality of manuscripts submitted even to the best of them, the decision to volunteer for a peer review or to decline respectfully is of paramount importance.  I personally would decline a review if either the subject matter is not of significant interest to me, or there is significant strain on time for the period allocated for the review by the journal. Of interest in the process of this decision to me also is the evaluation of potential conflicts of interest either declared or undisclosed by the authors. Such conflicts may directly arise from financial relationships of the author(s) to the subject matter of the manuscript – and often times from familiarity of the author with a ‘nominated’ peer reviewer as a professional colleague and/or a friend. Once I decide to review, the first piece of the manuscript that comes across is likely to be the abstract. Abstracts often are a window into the body of the manuscript – and merits close scrutiny. After all, most readers will likely read the abstract first as well. Needless to say that a quality manuscript should be able to invoke interest as well as provide evidence of scientific rigor even within the constraints of the word counts of the abstract. Simultaneously novelty of the investigation should well be portrayed through their abstract.

Next would come the introduction – this is supposed to lay the groundwork for the research details that follow subsequently in the script. However based on my own anecdotal experience, this is one of the least scrutinized segments for a peer reviewer in a rush. However, it may help to convey the logic as well as indicate prior work in the same area as the paper under consideration. That may even be unfamiliar to a seasoned peer review of the topic and may well be an educational treatise.

Then follows the methods section. Some degree of training and even mentoring can significantly help with the review of this section in my opinion. Journals should consider providing training in the various aspects of evaluating the methods section prior to enlisting a peer reviewer. Often times the journals do have statisticians/statistical consultants on their team/editorial board – however, imparting specific training for a volunteer peer reviewer who is considered an expert in a specific area of interest can potentially identify fatal conceptual errors which might otherwise be missed. For my purposes as a junior outcomes researcher without significant statistical training or expertise, I would recommend a statistician to review any part of a analysis plan that does not appear congruent.

Next for evaluation is the heart and soul – the results section of a manuscript. Of particular importance at this stage is to consider discarding/editing any redundancy – in the form of text, and/or figures and/or tables. Of great help to authors in improving a manuscript may stem from a reviewer’s suggestion of replacing any or all forms of the texts in the results with appropriate figures, and or tables with modifications of existing ones. More figures and tables may improve the readability of the manuscript as well.

Then comes the discussion section and it is here that the reviewer should decide if there is a thorough and balanced discussion of the results as reported in the previous section.  Evaluation of  references and adherence to the journal’s formatting criteria may have interest. Throughout the review process, help from a software to check spellings and grammar are of importance – may convey to the reviewer the lack of care and attention to details from the authors if there are too many.

Finally, enumerating ‘major’ vs ‘minor’ deficits may help overall evaluation. At the end of the peer review, there is the significant task of recommending a decision in the form of acceptance or revisions or rejection out right.  In most instances, the authors have dedicated significant effort and time – and deserve a fair and thorough evaluation leading to the decision.

The rewards for a detailed peer review are often a thank you note from the journal/editors, and more recently, CME credits have been a welcome addition. Some journals also list the peer reviewers in special issue. One idea that has been hotly debated for some significant time is the thought of having financial remuneration for peer review work – the idea being that reviewers would work as paid consultants to a journal. I don’t know how that may impact the quality of the process, but it may attract more interest upfront.

What are your thoughts?

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Race and In-Hospital Stroke Care

Intracerebral haemorrhage [ICH] accounts for ~15% of all strokes with an estimated 40% mortality at one month, with higher rates of occurrence among Black patients1. Differences have been observed in the burden of ICH by race, with a higher incidence among Black, Asian and Hispanic compared to White patients2,3.

The number of hospital admissions for ICH in the United States escalated from 150,000 in early 1990s to 175,000 in early 2000s2. Studies have reported racial differences in the quality and process of care among patients hospitalized with ICH4. A recent paper by Cruz-Flores found racial differences in In-hospital utilization of care including lifesaving and life-sustaining therapies, palliative care, do not resuscitate status and in-hospital mortality5.

Two recent studies showed that compared to whites, minority patients were more often younger with higher rates of medical comorbidities, longer length of stay and lower rates of do not resuscitate orders and in-hospital mortality2,5. Rates of hospital admissions have been also shown to be higher among minority men compared to women, however this might be a mere reflection of females not having equal access to care5.

A report on stroke performance measures by Xian in 2014 revealed smoking cessation counselling was less frequently completed among minority patients2. Counseling on modifiable risk factors is a key measure to reduce risk of stroke, recurrent stroke and coronary heart disease. In addition, Xian et al reported that Black patients were less likely than White patients to have a door to CT time of ≤ 25 minutes2. Rapid neuroimaging is one of the key class I recommendations of the American Heart Association/American Stroke Association for ICH patients2,6. Subsequent management is essentially dependent on identification of stroke subtype by neuroimaging. Further research is needed to identify mechanisms and causes of disparities in outcomes after stroke, ICH in particular, among minority patients.

 

REFERENCES

  1. Kleindorfer D, Khoury J, Moomaw CJ, Alwell K, Woo D, Flaherty ML, Khatri P, Adeoye O, Ferioli S, Broderick JP, Kissela BM. Stroke incidence is decreasing in whites, but not in blacks: a population-based estimate of temporal trends in stroke incidence from the Greater Cincinnati/Northern Kentucky stroke study. Stroke; a journal of cerebral circulation. 2010 Jul;41(7):1326.
  2. Xian Y, Holloway RG, Smith EE, et al. Racial/ethnic differences in process of care and outcomes among patients hospitalized with intracerebral hemorrhage. Stroke 2014; 45: 3243–3250.
  3. Woo D, Rosand J, Kidwell C, et al. The ethnic/racial variations of intracerebral hemorrhage (ERICH) study protocol. Stroke 2013; 44: e120–e125.
  4. Cruz-Flores S, Rabinstein A, Biller J, et al. Racial-ethnic disparities in stroke care: the American experience: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 2091–2116.
  5. Cruz-Flores, Salvador, Gustavo J. Rodriguez, Mohammad Rauf A. Chaudhry, Ihtesham A. Qureshi, Mohtashim A. Qureshi, Paisith Piriyawat, Anantha R. Vellipuram, Rakesh Khatri, Darine Kassar, and Alberto Maud. “Racial/ethnic disparities in hospital utilization in intracerebral hemorrhage.” International Journal of Stroke (2019): 1747493019835335.
  6. Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick JP, Connolly ES Jr, et al; American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010; 41:2108–2129.

 

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Alzheimer’s Disease: Prevention is the Best Treatment

Alzheimer’s disease (AD) is a progressive neurodegenerative condition and the most common cause of dementia. It accounts for about 60-80 % of all cases of dementia1. There are currently no curative or prevention therapies available for the disease. Medications prescribed for Alzheimer’s disease (AD) symptoms can temporarily help individuals with thinking, memory, or speaking skills and can help with some of the behavioral and personality changes associated with AD.  everal lines of evidence indicate that lifestyle habits and genetic factors play an important role in determining a person’s risk of developing AD2.

There have been a few recent disappointments with AD therapies when Biogen and Esai released negative results from a promising drug trial (3) and then Novartis, Amgen and Banner Alzheimer’s Institute announced in July their decision to not pursue further studies with a potential AD drug4. But new research presented at the Alzheimer’s Association International conference held in July at Los Angeles has provided evidence of a potential preventive strategy. Results from this study indicate that certain healthy lifestyle habits can reduce the risk of developing AD and even overcome the genetic risk in some susceptible individuals5.

During this retrospective cohort study,196 383 individuals aged at least 60 years, without evidence of cognitive impairment or dementia at baseline were followed for a median of 8 years. Risk assessment was performed using lifestyle and genetic risk scores. Lifestyle risk score was determined by a combination of smoking status, alcohol consumption, physical activity, and dietary habits. During the follow up period, a total of 1769 patients were diagnosed with new onset dementia. The incidence of dementia was noted in 1.23% of the high genetic risk group as compared to 0.63% in the low genetic risk cohort. The genetic risk was seen to be independent of the lifestyle factors.

About 68% participants followed a favorable lifestyle and 8% were noted to have an unfavorable lifestyle.

Dementia risk was seen to increase with worsening of lifestyle scores in a linear fashion. In the unfavorable lifestyle group, 1.16% persons developed dementia while 0.82% in the healthy lifestyle were diagnosed. Favorable lifestyle was associated with a lower risk of dementia despite an unfavorable genetic risk profile.

Favorable lifestyle habits in this study included: no smoking, limiting alcohol consumption to moderate levels, regular physical activity and maintaining a healthy diet. Regular physical activity was defined as per the American Heart Association (AHA) guidelines: 150 minutes of moderate or 75 minutes of vigorous activity per week (or an equivalent combination). This level of exercise, along with a healthy lifestyle, has also been associated with lowered risk of stroke and cardiovascular disease. Moderate alcohol consumption was defined according to the US dietary guidelines: 14g/day or less for women and 28g/day or less for men. Healthy diet was based on the dietary recommendations for maintaining optimal cardiometabolic health: this included regular consumption of at least 4 of the 7 food groups which constitute a healthy diet6.

This study provides evidence to support the benefits of a healthy lifestyle in reducing risk of dementia, even in individuals who may be at a higher genetic risk of developing dementia, including AD.  These results reinforce the American Heart Association’s healthy lifestyle recommendations for a healthy heart and healthy brain.

 

References:

  1. https://www.alz.org/alzheimers-dementia/what-is-dementia
  2. MangialascheF,KivipeltoM,SolomonA, Fratiglioni L. Dementia prevention: current epidemiological evidence and future perspective. Alzheimers Res Ther. 2012;4(1)
  3. http://investors.biogen.com/news-releases/news-release-details/biogen-and-eisai-discontinue-phase-3-engage-and-emerge-trials
  4. https://www.novartis.com/stories/discovery/stopping-alzheimers-disease-it-starts
  5. Ilianna Lourida, PhD1,2; Eilis Hannon, PhD1; Thomas J. Littlejohns, PhD3; et al. Association of Lifestyle and Genetic Risk With Incidence of Dementia. JAMA. Published online, July 13, 2019.
  6. Dietaryandpolicyprioritiesfor cardiovascular disease, diabetes, and obesity: a comprehensive review. Circulation. 2016;133(2): 187-225
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The Never Ending Art of Work-Life Balance

A philosophy professor places a large mason jar on the desk in front of his class and proceeds to fill the jar to the top with as many large rocks that will possibly fit. He then asks the class, “Is the jar full?” Some students answered yes, some answered no. It wasn’t full. So he continued to fill the jar with smaller rocks and then asks the class again, “Is the jar full now?” Again, the answer was no. So the philosophy professor adds sand to the jar and asks the question again. As before, the answer is no. This time he adds water to the jar and then asked his students:

“What is the moral of this story?”

“There’s always room for more,” one student cleverly commented. And while it was a good answer, it was incorrect.

“No,” the professor responded, “the moral of this story is that you should always put your big rocks in first or they will never fit.”

As I was sitting in this months Coffee with Women in Medicine and Science (WIMS) series titled, Work-Life Balance, this was my first time hearing about the Rocks, Pebbles and Sand Analogy for Time Management, and it really got me thinking. Throughout my undergraduate career, things came easy to me. I never had to use a planner. I never struggled to juggle, work, my campus leadership positions, class and friends. I had a strange gift of effortlessly making everything fit. Going into my third year of graduate school, lets just say that this is no longer the case.  By the end of the week, something, or someone, always gets left out of the equation. After hearing the stories of Women, at various stages of their careers, work and life is an equation that you are always trying to balance. An equation that can sometimes only become  harder once you decided to build a family in a workforce that tells women that children will only hinder their career.

My take away from this session, you can have it all. More importantly, my “all” may look different from  the next person’s “all” and that is okay. For some people, their family was their big rock, which meant home time was strictly family time, at least until the kids, and spouse, were asleep and if additional work needed to be done, then this was the time to do it. For others, that big rock was running, and making sure their was always sufficient time to get a decent long-distance run in. And for a few, that big rock was work. Sometimes, we may have deadlines, emergencies, or fellowships due that require time away from the “big rocks”. Whatever the case may be, the important thing is recognizing that you are putting the things that give you the most joy in life first.

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Pursuing Cardiology As a Medical Student/Resident

As an Early Career blogger for the AHA, I wanted to write my final blog post on advice for those interested in pursuing cardiology. My interest in cardiology began during my first year of medical school, and now as I am applying to become a fellow, I wanted to look back at the last 7 years.

 

Medical school

As a medical student, it can be difficult to know what field you would like to pursue. Although some may know from the beginning what they would like to specialize in, the majority of students must use their time during their clinical years to explore different fields. Given this, I would advise students to focus on getting a good background in all aspects of medicine during medical school. Take as much in from your exposure to each field. Do well on your boards, take ownership of the patients you see and read as much as you can.

So as a first or second year how can you know if cardiology is a field you should consider? Well, what made me interested in the field during those years was the physiology behind the mechanics of the heart.  It made intuitive sense. The time I spent reading Lilly’s Pathophysiology of Heart Disease did not feel like studying. This inspired me to sign up for electives in cardiology later on in medical school. During third and fourth year, rotating on a cardiology consult service or a CCU service can help you see the day to day life of cardiologist. It exposes you to the common consults and admissions in the field. It also allows you to get to know the type of personalities in cardiology. If you are interested, get involved in research projects.

 

Internal Medicine Residency

In the beginning of my residency, my advisor told me that before one could become a great cardiologist, they must become a great internist. This is something that I heard echoed by cardiology program directors during this past year’s AHA Scientific Sessions. A passion for patient care and an understanding of the intricacies of internal medicine are paramount in the path of a future cardiology fellow.

Be a good citizen in your program. Complete all your administrative duties on time. Be the one that chiefs can rely on when scheduling difficulties occur. Residency is not just about being smart but being reliable and hardworking. This makes you stand out.

While on the wards, incorporate the use of ultrasound in your daily practice. Try and volunteer for procedure and make it a goal to become comfortable with central and arterial lines.

Depending on your interests in cardiology, as a medicine resident it is worthwhile to get involved in a research project. It is important to truly have a passion for the research topic you decide to study. Whether it is because a patient you saw was affected by what you are researching, or if you have background in that topic, it is important to have a connection with the research topic. This is what drives you to spend your time outside of the hospital working on the research project. Attempting to work on a project in the name of “just having research” is a recipe for burnout and you will likely not complete the project.

Show case your research either through presentations at the AHA Scientific Sessions poster session or the American College of Cardiology meeting. Recognize that the deadline for abstract submission for these conferences are months before the meeting. Besides presenting, networking and sitting in on lectures important topics in cardiology. It is inspiring and will further your aspiration to work hard.

Finally, make sure to begin working on your application, specifically the personal statement early.

 

What was your experience applying to cardiology?

 

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Cardiovascular Maternal Morbidity and Mortality In the United States – What is the Cardiovascular State of Health for Pregnant Women and What is the Role of the Cardiologist?

Introduction

Despite advances in health care in the United States (US) maternal morbidity and morbidity remains significantly higher in the US relative to other developed nations with a reported maternal mortality of 14 per 100,000 live births in 20151.  Unfortunately, maternal morbidity and mortality rate has steadily increased over the last 2 decades2. The Centers for Disease Control (CDC) implemented the Pregnancy Mortality Surveillance System. The CDC defines a pregnancy-related death as the death of a woman while pregnant or within 1 year of the end of a pregnancy – regardless of the outcome, duration or site of the pregnancy–from any cause related to or aggravated by the pregnancy or its management, but not from accidental or incidental causes2.  Although the maternal morbidity and mortality rate declined in the 20th century, recent statistics have shown that this rate has increased more than 2 fold as the number of reported pregnancy-related deaths in the United States steadily increased from 7.2 deaths per 100,000 live births in 1987 to 17.2 deaths per 100,000 live births in 2015. More recent date has suggested that this rate is even higher at 26.4 per 100,000 live births3. Cardiovascular disease (CVD) accounts for approximately a third of pregnancy related deaths and is the leading cause of maternal morbidity and mortality2.  According to the American College of Obstetrics and Gynecology (ACOG) acquired heart disease is thought to be the cause for the rising cardiovascular mortality in women with an increasing number of mothers entering  pregnancy with a greater burden of common risk factors for CVD such as age, obesity, diabetes and hypertension2,3.

 

Disparities in Outcomes

There are also significant racial and ethnic disparities seen in maternal morbidity and mortality rates in the US with Black women having  a greater than 3 fold higher rate compared to White, non-Hispanic women (42.8 per 100,000 vs. 13 per 100,000 live births)2. The lowest maternal morbidity and mortality rate is seen in Hispanic women with a rate of 11.4 per 100000 live births. This rate progressively increases with White Non Hispanic women having a rate of 13.0 per 100,000 live births followed by 14.2 per 100,000 in Asians/Pacific Islander, 32.5 in American Indian Alaskan Native, and is highest in Black Non-Hispanic Women of 42.5 per 100,000 live births2 Figure 1.

The cause of this disparity is multifold and may also be related to a higher prevalence of CVD risk factors such as obesity and hypertension in Black non-Hispanic women4. There may also be limited access to adequate postpartum care in this patient population. There has been some action taken by ACOG with regards to providing recommendations for addressing these disparities5,6. However, there is a lot of work left to be done in resolving these inequities in maternal healthcare.

 

Role of the Cardiologist

It is vital that mothers who are at increased risk for CVD or have established CVD be referred to a Cardiologist for cardiovascular assessment and management in the early postpartum period. Therefore, raising the awareness amongst the Obstetrics and Gynecology community of this necessity of cardiovascular care in these women is important. Additionally, for us in the Cardiology community it is important to recognize these female patients when they present to us for the first time for care. Their presentation may be in the antepartum or postpartum period. In the antepartum period it is vital for us to be able to differentiate pathologic cardiovascular signs and symptoms from the physiologic cardiovascular changes related to pregnancy. It is also important that if these women present to us in the antepartum or postpartum period that they have an adequate assessment of their cardiovascular risk. Key historical features to obtain includes a thorough obstetrics history as there are several pieces of the obstetric history that may indicate a higher cardiovascular risk such as preterm deliveries, pre-eclampsia and frequent first trimester miscarriages. A systematic review and meta-analysis published in Circulation in 2018 by Grandi S, et al analyzed 84 studies that included more than 28 million women and had indicated that women with placental abruption and stillbirth in addition to hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm birth are at increased risk of future cardiovascular disease7  Figure 2. In addition to an obstetrics history, a family history of heart disease particularly premature heart disease is also important. These women should also be assessed for common CVD risk factors such as obesity, hyperlipidemia, diabetes, hypertension, smoking and a sedentary lifestyle. These risk factors should be appropriately and intensively managed through a combination of therapeutic lifestyle changes and medications where appropriate.

In the prepartum period women intending to become pregnant should also be screened  with regards to their CVD risk assessment and these risk factors should be appropriately managed to improve their overall CVD health prior to becoming pregnant. This is especially so as pregnancy could be viewed as nature’s stress test and the more cardiovascularly healthy women are when they conceive the more likely they will have better cardiovascular outcomes in the postpartum period.

In unique cases of women with Congenital Heart disease, it is imperative that these patients are seen by an Adult Cardiologist with expertise in Adult Congenital heart disease before considering pregnancy as there may be cases where women with certain Adult Congenital heart diseases or pathology such as Eisenmenger’s syndrome should be advised to avoid pregnancy. Additionally, there may be cases where therapies or procedures may have to be considered prior to becoming pregnant such as women with Marfan’s syndrome with significant aortic root dilation.

 

Solutions to the Problem

The rise in maternal morbidity and mortality in the US has been attributed to acquired CVD1 and is therefore preventable. In order to address this problem the following should be considered:

  1. Recognition and management of CVD risk factors in the prenatal Period
  2. Appropriate cardiovascular assessment in the prenatal period for women with congenital heart disease to determine if pregnancy is contraindicated and if not contraindicated to determine suitable follow up of these women in the ante and postpartum period. Appropriate delivery plan should be outlined in an appropriate tertiary high Obstetrics risk center with appropriate cardiovascular and neonatal services available.
  3. Adequate cardiovascular follow up during the pregnancy and postpartum period for women with an intermediate as well as a high CVD risk.
  4. A multidisciplinary Pregnancy Heart Team approach is important for women with intermediate and high CVD risk in the antepartum and postpartum period.
  5. Early postpartum period cardiovascular assessment is important in the first 1-2 weeks post delivery for women with high CVD risk features such as women with placental abruption and stillbirth in addition to hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm births.
  6. Women with high CVD risk should have long term cardiovascular care not only in the first year postpartum but these women will likely require long term cardiovascular follow up even beyond a year to improve their lifelong cardiovascular risk.
  7. Removal of barriers to access to appropriate prenatal, antepartum and postpartum cardiovascular care is important for all women regardless of race or ethnicity.
  8. Raising awareness of the elevated maternal morbidity and mortality risk predominantly due to CVD is important in both the Cardiovascular and Obstetric Gynecology medical community so that as providers we can deliver the best possible care to these patients to improve their outcomes.

 

Future Directions

With the increasing maternal morbidity and mortality in the US that has been attributed to CVD there is a role for increased collaboration between the Cardiologist and the Obstetrician with regards to a Pregnancy Heart Team. The role of this team is vital in improving CVD outcomes in the antepartum and postpartum period for these women. Hopefully the research collaborative called the Heart Outcomes in Pregnancy: Expectations (HOPE) for Mom and Baby Registry which aims to address key clinical questions surrounding the preconception period, antenatal care, delivery planning and outcomes, and long-term postpartum care and outcomes of women will help to address the knowledge gaps and disparities in the care of women with heart disease in pregnancy8.

There is also a need for greater risk prediction tools with regards to assessing CVD risk in the prenatal, antenatal and postnatal period. The recently concluded Cardiac Disease in Pregnancy (CARPEG II) study indicated that there were 10 predictors that could be utilized to assess maternal CVD risk9. These 10 predictors include:

  1. 5 general predictors;
    1. Prior cardiac events or arrhythmias (3 points)
    2. Poor functional class or cyanosis (3 points)
    3. High-risk valve disease/left ventricular outflow tract obstruction (3 points)
    4. Systemic ventricular dysfunction (2 points)
    5. No prior cardiac interventions (1 point)
  2. 4 lesion-specific predictors:
    1. Mechanical valves (2 points)
    2. High-risk aortopathies (2 points)
    3. Pulmonary hypertension (2 points)
    4. Coronary artery disease (2 points)
  3. 1 delivery of care predictor (late pregnancy assessment) (1 point)

Patients with a higher CARPREG II score had a higher incidence of adverse cardiac events in pregnancy.

It is hopeful that these new initiatives will assist providers in improving their ability to appropriately risk stratify women in the prenatal, antepartum and postpartum period with regards to CVD risk. Additionally, it is hoped that  these initiatives will also improve care of these women through improved collaboration between the cardiologist and the obstetrician.

 

 

References:

  1. World Bank Statistics -2018 https://data.worldbank.org/indicator/SH.STA.MMRT?locations=FI-VE&year_high_desc=false Accessed July 28, 2019
  2. Centers for Disease Control Pregnancy Mortality Surveillance System. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pregnancy-mortality-surveillance-system.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Freproductivehealth%2Fmaternalinfanthealth%2Fpmss.html Accessed July 28, 2019.
  3. American College of Obstetrics and Gynecologist (ACOG) Releases Comprehensive Guidance on How to Treat the Leading Cause of U.S. Maternal Deaths: Heart Disease in Pregnancy News Releases 2019. https://www.google.com/url?q=https://www.acog.org/About-ACOG/News-Room/News-Releases/2019/ACOG-Releases-Comprehensive-Guidance-on-How-to-Treat-Heart-Disease-in-Pregnancy?IsMobileSet%3Dfalse&sa=D&ust=1564343293391000&usg=AFQjCNGL5pYJww-2z_FrcgJuZhx4vTeRGA Accessed July 28, 2019.
  4. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O’Flaherty M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW, Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.Circulation. 2019 Mar 5;139(10):e56-e528. doi: 10.1161/CIR.0000000000000659
  5. American College of Obstetrics and Gynecology (ACOG) Committee Opinion No. 729: Importance of Social Determinants of Health and Cultural Awareness in the Delivery of Reproductive Health Care.Committee on Health Care for Underserved Women.Obstet Gynecol. 2018 Jan;131(1):e43-e48. doi: 10.1097/AOG.0000000000002459. Review.
  6. American College of Obstetrics and Gynecology (ACOG) Committee Opinion No. 649: Racial and Ethnic Disparities in Obstetrics and Gynecology.Obstet Gynecol. 2015 Dec;126(6):e130-4. doi: 10.1097/AOG.0000000000001213
  7. Grandi SM, Filion KB, Yoon S, Ayele HT, Doyle CM, Hutcheon JA, Smith GN, Gore GC, Ray JG, Nerenberg K, Platt RW. Cardiovascular Disease-Related Morbidity and Mortality in Women With a History of Pregnancy Complications. Circulation. 2019 Feb 19;139(8):1069-1079.
  8. Grodzinsky A, Florio K, Spertus JA, Daming T, Schmidt L, Lee J,
    Rader V, Nelson L, Gray R, White D, Swearingen K, Magalski
    A.Maternal Mortality in the United States and the HOPE Registry.
    Curr Treat Options Cardiovasc Med. 2019 Jul 25;21(9):42.
  9. . Silversides CK, Grewal J, Mason J, Sermer M, Kiess M, Rychel V,
    Wald RM, Colman JM, Siu SC. Pregnancy Outcomes in Women With
    Heart Disease: The CARPREG II Study J Am Coll Cardiol. 2018 May
    29;71(21):2419-2430

 

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BCVS 2019 Put Early Career Investigators at the Forefront

Attending conferences can feel overwhelming for young scientists because there’s a lot expected from us at these events — we’re supposed to learn the latest science, present our own work and make connections with potential collaborators or future employers.

It’s a lot.

Luckily, many meetings are building resources into the actual conference programming to help early career scientists with these daunting tasks. I was happy to see last week when I attended the American Heart Association’s Basic Cardiovascular Sciences (BCVS) conference, that the program was sprinkled with a multiple sessions specifically tailored for young scientists.

Attendees during the Early Career Investigator Social Event at AHA’s BCVS 2019 conference. Photo by © AHA/Todd Buchanan 2019

Attendees during the Early Career Investigator Social Event at AHA’s BCVS 2019 conference. Photo by © AHA/Todd Buchanan 2019.

Two sessions in particular called “Oh All the Places You Can Go … With a Degree” and “What I Wish My Mentor/Mentee Told Me” were a welcome change from the rest of the conference — and they were actually helpful.

Both events were career development panels, but they each had their own twist.

The “Oh All the Places You Can Go … With a Degree” panel had professors, a grant writer/instructor at a large cardiovascular institute and an industry scientist. The panelists’ diverse backgrounds and experiences allowed for an engaging discussion about the most effective way to start searching for a job, especially if you’re not looking to go the traditional academia route. This was particularly welcome since the chance of young scientists landing an academic position is insanely low. Young scientists need to be prepared for this environment.

During the “What I Wish My Mentor/Mentee Told Me” session, graduate students, postdocs and faculty talked about the academic side of mentoring — how to find a good mentor, how to be a good mentor and what to do if problems arise. Overall, I thought this session was interesting but most of the questions were geared towards the professor’s perspective. Also, it quickly became apparent that the participating professors were the actual mentors of the trainees on the panel, so it didn’t seem like an environment where the trainees could be completely honest about their work experiences because their bosses were sitting right next to them.

Both sessions were really well attended with almost every seat filled. I’m really excited to see events like these at future BCVS conferences and it seems like I’m not the only one.