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Hypertension and Stroke: Current State of Evidence

Stroke is the fifth leading cause of death in the country and the top reason for adult disability (1). Each year about 795,000 people experience a stroke in the United States with nearly 25% of these strokes being recurrent events in people with a prior history of a stroke (2).  Hypertension is the considered to be the most important modifiable risk factor for stroke. Therefore, treatment of hypertension is one of the most effective strategies for primary and secondary prevention of stroke (3). In a large meta-analysis from 2002, which included 1 million patients, a direct association was seen between blood pressure measurements and risk of vascular mortality including stroke and ischemic heart disease (4). There is a continuous relationship with risk throughout the normal range of blood pressure, down at least as far as 115/75 mm Hg according to this meta-analysis of 61 prospective clinical studies. However, there has been a lack of consensus among experts about the most appropriate blood pressure targets for cardiovascular disease and stroke prevention.

In the Secondary Prevention of Small Subcortical Strokes (SPS-3) trial, investigators compared systolic blood pressure targets of 130-149 mm Hg and less than 130 mm Hg (5). About 3000 patients with a recent history of an MRI confirmed lacunar stroke were randomized to one of the two treatment groups and followed for a mean of 3.7 years. Primary outcome of recurrent stroke was seen at a lower rate in the lower target group with an annualized stroke rate of 2.25% as compared to 2.77% in the higher target group. Despite a signal toward benefit of a lower BP target, these results did not reach statistical significance. The rates of intracerebral hemorrhage were noted to be significantly lower with a lower BP target.

In a clinical trial enrolling patients with diabetes and a high cardiovascular risk, blood pressure target of less than 120 mm Hg was not superior to a target of less than 140 mm Hg for reducing risk of cardiovascular events with the exception of stroke (6). In this study, the intensive blood pressure target lead to a significant risk reduction for stroke but not for myocardial infarction or all-cause mortality.

To further ascertain an ideal blood pressure target, investigators in the SPRINT trial enrolled over 9000 persons with SBP of more than 129 mm Hg without a history of diabetes (7). The participants were randomized to intensive treatment (target <120 mm Hg) or standard treatment groups (target <140 mm Hg). Primary outcome was a composite of myocardial infarction, heart failure, stroke or vascular death. After a median follow up of 3.3 years, the trial was stopped early due to a significantly lower rate of primary composite outcome in the intensive blood pressure group as compared to the standard treatment. Interestingly, even though there was a signal of benefit for stroke risk reduction, this was not statistically significant. The investigators of the study make note of this finding and hypothesize that this could be due to the fact that this trial excluded patients with a prior history of stroke and TIA. This has also raised questions about the limited applicability of these results to patients with a history of stroke.

The investigators also looked at cognitive outcomes for the two groups of patients in this trial (8). The composite outcome of mild cognitive impairment and dementia was seen in a significantly lower number of patients in the intensive BP treatment group as compared to the standard treatment group. Due to the early termination of SPRINT, the study was underpowered to show a significant difference in the risk of dementia.

The current guidelines (9) from the American Heart Association/ American College of Cardiology recommend initiating treatment at SBP>130 mm Hg for patients with a high cardiovascular risk. Using the current definition of hypertension, it is estimated that 46% of adults in the US have hypertension and about 36% should be prescribed antihypertensive medications (10). Applying these new guidelines, only about half of all US adults on medications for hypertension are currently below the target BP numbers.

With hypertension playing such an important role in the development of the two most common neurological illnesses (Stroke and cognitive disorders), authors of a recent paper in JAMA Neurology (11) urge neurologists to play a greater role in treatment of hypertension as a preventive strategy for their patients. Traditionally stroke neurologists and neurointensivists have been involved in treatment of the cardiovascular risk factors including hypertension but most of that is done after the patient has had a major event such as an ischemic stroke or intracerebral hemorrhage. The authors argue that neurologists should participate in treatment of hypertension for their patients as a primary preventive strategy as it would lead to an overall improved brain health of our ageing population.

To learn more about the latest advancements in the field of hypertension research, I encourage the readers to attend Hypertension 2019 Scientific Sessions being held in New Orleans September 5-8, 2019.

 

References:

  1. Vital Signs: Recent trends in stroke death rates – United States, 2000-2015. MMWR 2017;66.
  2. Benjamin EJ, Blaha MJ, Chiuve SE, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation. 2017;135:e229-e445.
  3. Katsanos AH, Filippatou A, Manios E, et al. Blood pressure reduction and secondary stroke prevention: a systematic review and metaregression analysis of randomized clinical trials. Hypertension. 2017;69(1):171-179.
  4. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies Lancet. 2002;360(9349):1903-1913.
  5. Benavente OR, Coffey CS, Conwit R, et al; SPS3 Study Group. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 2013;382(9891):507-515.
  6. Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-1585
  7. Wright JT  Jr, Williamson  JD, Whelton  PK,  et al; SPRINT Research Group.  A randomized trial of intensive versus standard blood-pressure control  [published correction appears in N Engl J Med. 2017;377(25):2506].  N Engl J Med. 2015;373(22):2103-2116.
  8. Williamson JD, Pajewski NM, Auchus AP, et al; SPRINT MIND Investigators for the SPRINT Research Group. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial.JAMA. 2019;321(6):553- 561
  9. Whelton PK, Carey RM, Aronow WS, et al.
  10. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127-e248.
  11. Muntner P, Carey RM, Gidding S, et al. Potential US population impact of the 2017 ACC/AHA high blood pressure guideline. Circulation. 2018;137(2): 109-118.
  12. Betjemann J, Hemphill JC, Sarkar U. Time for Neurologists to Drop the Reflex Hammer on Hypertension. JAMA Neurol.Published online August 19, 2019. doi:10.1001/jamaneurol.2019.2588
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Telemedicine May Play A Role In Rural And Urban Community Engagement

Telemedicine may be the original term for remote patient care management using telecommunications beyond a phone call, but telehealth is also used. While the two terms are often used interchangeably, one could propose that telehealth could encompass more of a wellness approach that is proactive than the typical reactive nature of medicine. Traditionally, we have focused predominantly on management of disease. Yet, it may be more prudent and cost-effective to focus even more so on health, wellness, and prevention of disease. Nevertheless, for the purpose of this article, the term telemedicine will be used.

Many institutions are now pursuing telemedicine, or are planning to do so in the near future. Of course, several hospitals and medical systems are appropriately concerned about reimbursement. Reimbursement currently associates with more rural communities. However, there is also a role for telemedicine in less rural neighborhoods. If we are to ubiquitously implement telemedicine equitably, we may need to remove those boundaries of rural versus not, in telemedicine allocation decision-making. We need to be great stewards of our healthcare resources, and we need to determine where to best direct our efforts. Rural communities may benefit most from telemedicine, but other communities can as well. Perhaps in the most urban communities, telemedicine might be needed much more than anticipated. It is often in urban communities that we find limited community engagement with nearby health centers. Would the level of community engagement with health care centers in urban communities improve if telemedicine were more available in these areas? Availability and feasibility would depend on the source of provision and financing of the tools needed for telemedicine. These tools would include at a minimum internet access, computers or smart phones, physiology monitoring and diagnostic equipment, and free or costly apps. It should be recognized that telemedicine itself alone cannot effect community engagement. In fact, community engagement itself would be needed for adoption of telemedicine throughout the community. It might seem like a circular argument, because it is.

We often attempt to practice medicine or innovate in silos. Yet, it is when we remove the boundaries between the silos or blur the lines between neighborhoods and cross-pollinate that we can find nonlinear progress. Synergy can be found in the overlap of various kinds of disruptive innovation. Synergy can also be found in the overlap between the perspectives of community dwellers and healthcare professionals and innovators. Healthcare research and practice is now moving towards greater incorporation of the patient voice, choice, desires, values, and goals, not as bystanders, but as drivers. Not only should we take this approach at the level of the individual patient, but at the level of the population or community. Thus, community engagement is needed for adoption of telemedicine, and telemedicine itself perhaps may help to further catalyze community engagement. It therefore appears that telemedicine is not only about providing care for the individual patient in their home, whether due to patient location or mobility or simply patient preference. It would seem that telemedicine is also about providing care for the population and a community and enhancing relationships among community dwellers and their healthcare providers. This would potentially apply to rural, urban, and also global communities and populations.

It may also be more cost-effective to pursue telemedicine for patients in both rural and urban areas locally, regionally, nationally, and globally, before our patients in urban and rural communities become unwell and need to be hospitalized. Overall, medicine is very slowly moving towards prevention. Telemedicine could facilitate disease prevention in urban, rural, and global populations, as well as joint management of the most remote locally hospitalized patients before their inpatient status worsens. This could limit morbidity and mortality and decrease health care costs in the long run.

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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

`

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?