hidden

Artificial Intelligence in Cardiology: Opportunities for Cardio-Oncology

History was made recently with the inaugural and first ever continuing medical education conference on artificial intelligence (#AI) in Cardiology. While most of the presentations were on artificial intelligence or cardiology or both, several sessions also made reference to other fields in which AI has been or is being used, such as Oncology. There was even one study presented on Cardio-Oncology. As study after study was presented, it became clear to me that perhaps several of these techniques and methodologies could potentially be useful to our patients in Cardio-Oncology.

Every single piece of technology started with one single prototype. Every single new piece of software started with one single algorithm. Every single patent started with one single idea. Every single idea started with the impact that disruptive technology could have for at least one single patient – one single case.

As I view various case reports in Cardio-Oncology, I think about how #AI could influence care delivery to potentially improve outcomes and the experience for each patient and their health professionals.

One example that was reiterated in multiple presentations was that of the ECG. Applying #AI to the ECG has been shown in the studies presented to determine the age, sex, and heart condition of the individual. Details were shown for a case of hypertrophic cardiomyopathy (yes, HCM, not just left ventricular hypertrophy) diagnosed via #AI analysis of an ECG that appeared relatively unremarkable to physicians’ eyes. After the septal surgery/procedure, although the ECG then looked remarkably abnormal to physicians’ eyes, the #AI algorithm could identify resolution of the hypertrophic cardiomyopathy.

Another example reiterated throughout the conference was identifying undiagnosed left ventricular systolic dysfunction, in a general community population and also in patients referred to a cardio-oncology practice at a large referral center.

Recently, #AI in Cardiology has been used most frequently for monitoring and detection of arrhythmias, such as atrial fibrillation. Everyone can purchase their own wearable to determine this. Physicians are also now prescribing these wearables for ease-of-use, given their pervasive presence and coupling with smartphones owned by much of the population or provided temporarily by the physician group. Such wearables are transitioning from standalone electrodes, to watches, skin patches, and clothing (e.g., shirts, shorts).

Many direct-to-consumer #AI applications in daily life actually are not wearable, such as Alexa and Siri. One study described the ability of #AI to help diagnose mood disorders and cardiac conditions and risk factors by simply “listening to” and analyzing voice patterns. The timing of a young man’s “voice breaking” can potentially predict his risk for heart disease!

A popular use for #AI in medicine overall is to assist with interpretation of various imaging, such as chest X-rays, MRIs, or CT scans. This applies in Cardiology as well. Further, in Cardiology, #AI is being used to help guide the procurement of echocardiograms. The algorithms provide visual instructions (such as curved arrows) to indicate directions in which the ultrasound probe should be moved to obtain the standard view, to which the algorithm is comparing the image being procured moment-by-moment. The idea is for #AI to help less experienced sonographers or echocardiographers learn and perform echocardiography even more expediently.

The theme of the conference was current advances and future applications of #AI in Cardiology. Accordingly, a historical perspective was given, describing some of the earliest attempts at #AI in various fields. A video of a possible precursor to current automated vacuum cleaners was shown, from archives dating back to the 1960s. In addition to ways in which #AI is now being studied or applied, future opportunities for using #AI were also postulated, for example for coronary artery disease, since stress tests are not 100% sensitive and the gold standard coronary angiography is invasive. #AI could help stratify patients who needed versus did not need the invasive procedure for recurrent convincing symptoms in the absence of a positive stress test. Of course, coronary CT angiography could help fill this gap, but #AI might assist with decision-making sooner.

There have been studies on #AI in Cardiology, and studies on #AI in Oncology, and at least one study in #AI in Cardio-Oncology – a study I predicted; one that is quite intuitive and mentioned above. I propose that we continue to apply #AI in Cardio-Oncology, so that the field can catch up with the rest of Cardiology and Oncology, and help us continue to develop this emergent and burgeoning multidisciplinary subspecialty.

This is an exciting time for me to be alive. I am an early adopter of artificial intelligence. I look forward to seeing more and more the availability of #AI to enhance our use of electrocardiography, echocardiography, wearables, biosensors, voice analysis, and more in Cardiology, and particularly in Cardio-Oncology, with an emphasis on primary and primordial prevention even before secondary and tertiary prevention in the area of Preventive Cardio-Oncology, and especially in women.

 

 

 

hidden

Atrial Structure and Function – Methodology of Atrial Strain

“If echocardiographers are to stand still, depend on standard 2D echo imaging using equipment produced a decade ago and not upgraded since, perform “ejectionfractionograms,” focus primarily on the left ventricle and simply ‘‘eyeball’’ the other chambers, and avoid new methods such as strain imaging and contrast echo because they are perceived as ‘‘a waste of time’’, then I fear that echocardiography will be passed by. As the dinosaurs illustrated, we need to adapt and continue to evolve, or face the consequences.”   –Alan Pearlman- JASE editor, 2010

My research experience focused on heart failure and atrial function. I conducted medical research on the derivation and validation of novel echocardiographic approaches to myocardial and atrial deformations. I have been heavily involved with all projects using strain echocardiography at Duke University (approximately 50 projects over the last 7 years). I have completed over 10,000 speckle tracking strain measurements analysis on different cardiac diseases and on different cardiac chambers.

Both left and right atrium function moderate ventricular function through three components:

  1. Atrial diastole (Reservoir phase) or expansion during ventricular systole. This function is dependent on ventricle longitudinal function, atrial wall elastance and venous return. Reservoir function may increase during physical activity in a normal healthy heart. Increase of this phase help to increase ventricular filling.
  2. Passive atrial systolic phase (Conduit function) during ventricle early diastole. This phase is dependent on the ventricle end-diastolic pressure. Conduit function does not affect by physical activity.
  3. Active atrial systolic phase (Active contraction) (when sinus rhythm is present) during ventricle late diastole. This phase is dependent on atrial wall contractile properties and ventricular end diastolic pressure. Active contraction function is affected by physical activity in a normal heart.

Traditionally atrial function was measured indirectly by using volumes. However, this is still not resembling the actual atrial deformation and mechanics. With a high feasibility and reproducibility of speckle tracking strain echocardiography, atrial function is ready to be a part of an echo report in a daily clinical practice.

Speckle tracking strain imaging has been around for quite a while and we celebrated the first decade 3 years ago, whereas the technique described in 2004 (Leitman M-JASE) and clinical applications appeared around 2005 (Notomi Y- JACC). Since then, the interest has risen dramatically and so far, we have > 5000 publications on this topic. Left ventricular (LV) ejection fraction (LVEF), the most widely used measure of cardiac function, has important limitations including low sensitivity for incident HF, technique-related variability and does not directly assess LV contractility. Global longitudinal strain (GLS) is the most studied among strain parameters and its prognostic value has been demonstrated in several clinical scenarios.

GLS inter-Vendor variety has dramatically dropped over a short period of time. However, still if we look at the same images with different software vendors, we may have different values. This difference is due to several factors: 1) Image quality and acquisition; 2) Software used; 3) Where to measure (endocardial, myocardial, median); 4) Post-processing of data; 5) Patients age, gender variabilities and loading conditions. With regard to regional (segmental) function, we now have, for the first time, the possibility to measure regional myocardial function. However, I think this is more challenging than GLS, and there is still progress to be made. The challenges become because we have only one segment to work with, and less data to average. Tracking quality becomes more important, regional artifacts matters more, definition of sample position more relevant, and more importantly, we cannot simply measure peak values anymore. For regional analysis, the strain curve shape (not peak values, because peak values can be the same), become critical.

atrial function and structure

Technical factors that may influence atrial strain values:

  • Optimization of images quality and frame rates are vital (ideally, no less than 40 fps).
  • Start tracing at the lateral valve annulus, along the endocardial border of the atrial lateral wall, atrial roof, atrial septal wall, and ending at the septal valve annulus.
  • Difficulties tracking atrial segments relate to the thin wall, insertion of blood vessels and atrial appendages.
  • Significant age-related reductions in strain have been reported. Similarly, sex-related differences have been described, with lower deformation noted in male patients than in female patients.
  • Atrial strain increases in response to early physiological heart rate increase in the setting of exercise in normal patients. However, decreased values are found in the setting of pathological heart rate increase.
  • Atrial strain also affected by loading condition. Reporting, BP, HR and heart rhythm, IVC diameter are crucial.
  • Atrial phases function (Reservoir, conduit and atrial) is also dependent on the ventricular function. Report both atrial and ventricular functions are important.
  • Atrial strain maybe useful as an early marker of DD.

In summary, I think GLS is ready for clinical practice. Its robust, reproducible and has been shown to add unique data that can guide diagnosis and management. I recommend GLS as a valuable complement to traditional function parameters. Further studies are needed to standardize vendors, recognizing specific strain patterns and to determine if there are age, gender variabilities or loading conditions difference.

 

References:

Myocardial Strain Measured by Speckle-Tracking Echocardiography: Patrick Collier, MD, PHD, Dermot Phelan, MD, PHD, Allan Klein, MD VOL. 69, NO. 8, 2017 – ISSN 0735-1097

hidden

Cardiac Longitudinal Function: GLS vs. MAPSE

Over the history of echocardiography, there have been a multitude of research studies on the feasibility, reproducibility and the prognostic values of different echocardiographic parameters in different disease groups. Fifty years later, no single echocardiographic parameter is unique for assessment of the cardiac structure and function. Even the most widely used measurement for left ventricle ejection fraction (LVEF) has important limitations, including low sensitivity for incident heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). With the advent of speckle tracking echocardiography (STE), early detection of cardiac dysfunction before signs or symptoms of HF develop (stage A or B HF) has become a target of many researchers in the last 15 years. Although, there has been some success, there is still a long way to go. In this blog, I want to discuss the differences, advantages and the limitations of mitral annular plane systolic excursion (MAPSE) vs. global longitudinal strain (GLS).

MAPSE measures LV longitudinal shortening and it has been around for over 50 years. Reduction in MAPSE was described as a marker of LV dysfunction (Figure 1). Nowadays, newer and more refined echocardiographic technologies, such as strain, are used more widely for assessment of LV function and deformation. STE imaging has been around for quite a while and we celebrated it’s first decade just 4 years ago, whereas the technique described in 2004 (Leitman M-JASE) and clinical applications appeared around 2005 (Notomi Y- JACC). Since then, the interest has risen dramatically and so far, we have around 6,000 publications on this topic. GLS is the most studied among strain parameters and its prognostic value has been demonstrated in several clinical scenarios.

Figure 1: GLS vs. MAPSE – Fawaz Alenezi -2019.

 

MAPSE (cm) GLS (%)

Technique

  • Real time or reconstructed M-mode
  • Measure mitral annular displacement
  • Speckle tracking
  • Measure myocardial deformation
Advantages
  • Less dependent on image quality and almost (> 95%) is feasible
  • Good correlation with LVEF
  • Simple and fast
  • Excellent reproducibility
  • High temporal resolution
  • More standardized
  • Better than LVEF in some cases
  • Vendor independent
  • Not gender or BSA dependent
 

  • Assess regional and global longitudinal/radial/circumferential function, rotation/torsion, and ventricular synchrony
  • Less angle dependent
  • Better than LVEF in some cases
  • Good correlation with LVEF

 

Disadvantages
  • Unable to detect regional abnormalities
  • Angle dependent
  • Age dependent
  • Pericardial effusion: The interpretation of MAPSE should be carefully applied in case of a mobile apex.
  • RV dysfunction: In patients with paradox septal motion, septal MAPSE is not only reflecting LV function but rather RV abnormalities
  • Mitral valve disease and ring calcification: Sometimes in patients with mitral valve disease, the mitral ring is extremely calcified. In these patients, the direct MAPSE measurement at the mitral ring is not possible and longitudinal functional assessment should be done slightly more above in the myocardium
  • Septal MI: Another limitation of this parameter is that small localized abnormalities (i.e. small areas of fibrosis) cannot be detected as it is only possible to assess longitudinal function of the complete wall
  • LVH: In patients with LVH due to HTN or AS will have different values
 

  • Vendor dependent
  • Although, assessment of regional function is the main advantages of strain, but studies still showing a large variability and is not ready to clinical use
  • Variable in region of interest definition
  • Highly dependent on image quality
  • Gender and BSA dependent
  • Need experience and time consuming
  • Pre and after load dependent
  • Rhythm and rate dependent
  • Frame rate dependent

Table 1: Advantages and limitations of GLS vs. MAPSE- Fawaz Alenezi – 2019

 

What is thought to be the main advantage of STE over MAPSE is the ability of global and regional function assessment. However, with regard to regional (segmental) function, I think this is more challenging and there is still progress to be made. The challenges exist because we have only one segment to work with and less data to average. Tracking quality becomes more important, regional artifacts matters more, definition of sample position more relevant, and more importantly, we cannot simply measure peak values anymore. For regional analysis, the strain curve shape (not peak values, because peak values can be the same) become critical. Regional strain measurements have much higher variability among vendors when compared with GLS. Recently, the HUNT study (Stoylen A et al. 2018 –Wiley echocardiography journal) showed that MAPSE and GLS measured both as MAPSEn (n= normalized for end diastolic length) and GLS have similar biological variability in adults without improvement by normalizing for length for both.

In summary, I think both GLS and MAPSE are measuring the same cardiac function. GLS is robust, reproducible and has been shown to add unique data that can guide diagnosis and management. However, it is vendor, image quality and hemodynamics dependent that need more standardization and experience. On the other hand, MAPSE is simple, easy, available in every echo machine and, more importantly, feasible even in a poor image quality. But it is not measuring the global function. Further studies are needed to standardize vendors, recognize specific strain patterns, determine if there is loading conditions difference and head-to-head comparison between both methods.

 

hidden

A Personal Experience in Developing A Risk Prediction Algorithm

Selection of Patients for Systemic Thrombolysis in Pulmonary Embolism (PE)

Selecting the correct patient for systemic thrombolysis necessitates a thorough assessment of the patient’s preexisting comorbidities, mode of presentation and focused clinical examination to assess the immediate risk of hemodynamic collapse, the risk of long term complications, and the risk of major bleeding associated with the thrombolytic agent. As described above, high-risk PE patients warrant strong consideration of aggressive treatment options, including systemic thrombolysis with a high incidence of adverse outcomes if not instituted expediently. In patients who present with acute high-risk PE, the risk of mortality is high which makes the decision for systemic thrombolysis relatively easier as compared to the people who are hemodynamically stable. The case fatality of these hemodynamically unstable patients ranges from 35% to 58%. Therefore, benefits clearly outweigh the risk of adverse outcomes in the grand majority of high-risk PE patients who are not experiencing severe active bleeding.

Clinical Assessment:

Ideally, a prognostic model should be able to precisely identify the risk of mortality and recurrent PE in patients so that escalation of treatment can be performed when necessary. Also useful would be a risk model that predicted risks of various therapies beyond anticoagulation. Various risk predicting tools have been described in the literature with the Pulmonary Embolism Severity Index (PESI) (Table 1) being the best validated to determine short term mortality (30-day) in patients with PE. This prognostic model classifies patients from risk Class I (very low risk) to Class V (very high risk) based on demographics (age and sex), comorbidities (history of cancer, heart failure, chronic lung disease), and clinical findings (mentation, oxygenation, blood pressure, pulse and respiratory rate). Mortality risk ranged from 1% in Class I patients to 24.5% in Class V patients. With most patients falling in Class II and Class III, the negative predictive value reaches above 90% in low risk patients (Class I-III). Modified PESI was also introduced which is a simpler version of above described PESI with similar predictive precision but simpler to use. It includes age, history of heart failure or cancer and blood pressure, pulse rate and oxygen saturation.Both prognostic models can be used to risk stratify patients who can be eligible for thrombolytic therapy, but these models failed to predict the risk of adverse outcomes in these patients. In fact, there is no well-validated prediction model to assess the risk of bleeding in patients receiving thrombolysis for PE. Therefore, absolute and relative contraindications for thrombolytic therapy along with clinical judgment are the only tools available to risk stratify for bleeding.

 

Pulmonary Embolism severity Index (PESI) Simplified Pulmonary Embolism Severity Index (sPESI)
Demographics Demographics
Age >80 years Age >80 years
Male Sex
Comorbidities Comorbidities
History of Heart Failure History of cancer
History of cancer History of chronic lung disease
History of chronic lung disease
Clinical findings Clinical findings
Tachycardia>110 beats/min Heart Rate> 110/min
Systolic blood pressure <100 mm Hg Systolic blood pressure <100 mm Hg
Respiratory Rate >30/min Arterial oxygenation saturation <90% (with or without supplemental oxygenation)
Temperature <36 C
Altered mental status (lethargy, stupor, Coma)
Arterial oxygen saturation <90% (with or without supplemental oxygenation)

Table 1: Original and simplified pulmonary embolism severity index (PESI) (prognostic model to predict 30-day outcomes in patients with acute pulmonary embolism)

 

Biomarkers and Imaging assessment:

Rise in cardiac biomarkers, including troponin and brain-type natriuretic peptide (BNP) may represent right heart dysfunction and have been associated with an increased risk of PE related deaths. Chest CT scan is the gold standard imaging modality for patients who come to the ED with suspicion of PE. Easy-to-measure dimensions can be prognostically important in selecting patients who are at elevated risk of early deterioration.

Bedside transthoracic echocardiography can be utilized to detect RV dysfunction in the setting of acute PE. It can detect a  wide range of imaging indicators form very nonspecific right ventricular dilatation and hypokinesis to the very specific McConnell’s sign, in which the right ventricle has a characteristic appearance of significant enlargement with free wall dysfunction and relative apical sparing. Echocardiography should be performed to further risk stratify patients with clinical evidence of RV failure, elevated cardiac enzymes or in clinical decompensation. All these modalities can be helpful in not only classifying these patients as intermediate or high risk patients but also to segregate patients with high likelihood of early deterioration so that systemic thrombolysis can be utilized.

Summarizing the patient selection criteria for systemic thrombolysis, it is clear that the clinical judgment to utilize a thrombolytic agent in addition to anticoagulation in a patient with acute PE necessitates an individualized assessment of the benefits  of improving morbidity and mortality versus risk of major bleeding.

 

Absolute Contraindications Relative contraindications
§  Prior intracranial hemorrhage §  History of chronic severe uncontrolled hypertension
§  Known structural cerebral lesion §  Severe uncontrolled hypertension (systolic >180 mmHg or diastolic >110mmHg
§  Known malignant intracranial neoplasm §  History of ischemic CVA >3 months
§  Ischemic stroke within 3 months §  Trauma or prolonged CPR >10mins
§  Suspected aortic dissection §  Major surgery within 3 weeks
§  Active bleeding (excluding menses) §  Recent internal bleed (2-4 weeks)
§  Significant closed-head or face trauma within 3 months §  Pregnancy, active peptic ulcer, pericarditis, age>75years, diabetic retinopathy, recent invasive procedure, current anticoagulant use

Up to two third of acute PE patients do not receive thrombolytic therapy due to contraindications.

Table 2: Contraindications to systemic thrombolysis in acute pulmonary embolism patients

 

Often patients with acute pulmonary embolism (PE) do not receive thrombolytic therapy even if they could potentially benefit from such, mainly due to concerns for bleeding, especially intracranial hemorrhage (ICH).There are no known risk predictor algorithm(s) for assessing ICH risk in PE patients. A simple, novel risk score was developed to predict ICH in patients with PE treated with thrombolytics – the risk predictors including peripheral vascular disease (P), age>65 (Elderly-E), prior stroke (CVA-C) and prior heart attack (H)-components of the PE-CH score. The strongest risk predictor was a history of prior stroke, including both ischemic and hemorrhagic.

This is the first risk assessment algorithm to look at ICH risk in PE patients-future research should be directed towards refining this initial risk score by incorporating laboratory and radiographic parameters for optimal risk prediction. For patients, and healthcare providers alike, the risk score provides an easy opportunity to evaluate the risk of ICH for patients with acute PE being considered for thrombolytics. The PE-CH score provides an initial risk prediction model for ICH risk in patients with PE receiving thrombolytics. In patients with more than one risk predictor, especially those with a prior history of stroke, great caution must be exercised prior to consideration of thrombolytic use.

 

Reference:

Thromb Haemost 2017; 117(02): 246-251
DOI: 10.1160/TH16-07-0588

 

hidden

The Significant Areas of Interest in the Field of Cardiac Imaging in 2018

There were several exciting developments in 2018 with regards to cardiac imaging. The role of the cardiac imager is becoming increasingly relevant in today’s cardiology practice environment and bridges across several subspecialties in Cardiology, such as electrophysiology with the use of transesophageal echocardiography (TEE) in the placement of left atrial appendage closure devices. These devices include Watchman and interventional cardiology with structural and valvular heart disease and echocardiographic guidance with transaortic valve replacement (TAVR), percutaneous mitral valve repair with MitralClip, as well as atrial septal and ventricular septal closure devices. The field of cardiac imaging has matured over the years and not only includes echocardiography and nuclear cardiology, but also includes advanced imaging with cardiac magnetic resonance imaging (cMRI) and cardiac computed tomography. In addition, there has been the rise of the interventional echocardiographer specializing in the use of echocardiography in guiding percutaneous and surgical treatment of structural heart disease. In fact, there has been recognition of cardiac imaging by several professional societies such as the American College of Cardiology with publication of the state-of-the-art paper, The Future of Cardiac Imaging Report of a Think Tank Convened by the American College of Cardiology1. There have also been several disease states that have been positively influenced by the development of new diagnostic technology in cardiac imaging, such as cardiac amyloidosis. Cardiac imaging has also positively influenced preventive cardiology with release of the latest American Heart Association (AHA)/ American College of Cardiology (ACC) 2018 Cholesterol Management Guidelines2. The following areas were, in my opinion, considered topics of great interest in 2018 in the field of cardiac imaging.

 

Nuclear Imaging

Cardiac Amyloidosis. For several years, cardiac amyloidosis, particularly transthyretin type (ATTR type), was thought to be a diagnosis that was very difficult to make with endomyocardial biopsy being the only method to confirm the diagnosis. However, nuclear cardiac imaging has changed the landscape of this disease with the novel application of old technology with the use of technetium 99m pyrophosphate (Tc-99m PYP) in the diagnosis of ATTR type cardiac amyloidosis3. The sensitivity and specificity of this technique in diagnosing this disease state is >95%, and oftentimes avoids the need for endomyocardial biopsy to make this diagnosis4. The development of this technique in diagnosing the disease has increased the recognition of this disease in many patients with diastolic heart failure, and even in patients with severe aortic valve stenosis undergoing TAVR. This has also led to greater research and development of new treatments for this disease, such as tafamidis, patisiran and inotersen. The development of these medications will hopefully improve the overall prognosis for patients with this disease.

 

Echocardiography

The Rise of the Interventional Echocardiographer in Structural Cardiac Imaging. There has been increasingly relevant areas of interest in structural heart disease, such as percutaneous mitral valve repair with MitralClip, especially with the release of the study findings from the COAPT trial5.  In addition, transaortic valve replacement (TAVR) has become increasingly available for many patients with severe aortic valve stenosis, and many institutions have began offering this therapy to many of their patients. Additionally, left atrial appendage occlusive devices such as the Watchman device are being increasingly used in patients with atrial fibrillation who are at high risk for hemorrhagic complications with anticoagulation, despite having indications for thromboembolic prophylaxis. With these new developments, there has been the rise of the interventional echocardiographer, who serves a vital role with the use of echocardiography in guiding the placement of these devices in the treatment of structural heart disease. Many fellows are now seeking additional training in this field to meet this demand, as this area has invited a growing interest in the cardiology field and has attracted many trainees.

 

Cardiac Computed Tomography

The revisiting of Coronary Calcium Score as a Powerful Tool in Preventive Cardiology. The release of the latest AHA/ACC Cholesterol Management Guidelines has been an area of great interest in the field. The latest guidelines have included the use of coronary calcium scoring with cardiac CT as a tool to further risk stratify patients to guide the use of pharmacologic therapy for patients with hyperlipidemia2. This has led to  the resurgence of Cardiac CT for coronary calcium scoring as a valuable tool for cardiologists in the field of preventive cardiology.

Utility of Cardiac CT in the assessment of Women with suspected Cardiovascular Disease.  There has also been the increasing recognition of Cardiac CT as a useful diagnostic tool for women suspected of having cardiovascular disease (CVD)6. Hopefully, this will result in the increased appropriate use of Cardiac CT in the management of CVD in women.

 

Cardiac MRI

The complementary role of Cardiac MRI with echocardiography and assessment of valvular and structural heart disease. Cardiac MRI has become an established imaging modality in the assessment of valvular heart disease. This has been embraced by the American Society of Echocardiography’s latest Valvular Guidelines, which includes cardiac MRI as playing a complementary role in the assessment of the severity and etiology of valvular heart disease7. The use of Cardiac MRI is also useful in the assessment of other disease states, such hypertrophic cardiomyopathy and risk assessment for sudden death8.

The rise of Cardiac MRI compatible devices. There has also been the development of Cardiac MRI compatible devices which now allows many patients with these devices to be able to have cardiac MRIs performed safely. Cardiac MRI is therefore a viable diagnostic tool for these patients.

The first administration of certification board exam in cardiovascular magnetic resonance imaging (CBCMR).  With the maturation of Cardiac MRI as a viable imaging modality, 2019 will see the inaugural administration of the first certification exam in cardiovascular magnetic resonance imaging (CBCMR), which will occur between May 7 – June 7, 2019, and the 2019 application window will open on January 15, 2019. ​​

 

Conclusion:

With the dawn of a new year in 2019, it is clear that the future of cardiac imaging is very bright. I am looking forward to many more promising developments in this field and hope that this field will continue to attract many more talented cardiologists in this area of cardiology.

 

References:

  1. Douglas PS, Cerqueira MD, Berman DS, Chinnaiyan K, Cohen MS, Lundbye JB, et al. The Future of Cardiac Imaging Report of a Think Tank Convened by the American College of Cardiology. J Am Coll Cardiol Img 2016;9:1211–23.
  2. Grundy SM, Stone NJ, Bailey AL, Beam LT, Birtcher KK, et al. 2018AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. JACC Nov 2018, 25709; DOI: 10.1016/j.jacc.2018.11.003.
  3. Dorbala S, Bokhari S, Miller E, Bullock-Palmer RP, Soman P, Thompson R. ASNC Practice Points: 99mTechnetium-Pyrophosphate Imaging for Transthyretin Cardiac Amyloidosis (American Society of Nuclear Cardiology website). 2018. Available at: https://www.asnc.org/Files/Practice%20Resources/Practice%20Points/ASNC%20Practice%20Point-99mTechnetiumPyrophosphateImaging2016.pdf.
  4. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016 Jun 14;133(24):2404-12. Doi: 10.1161/CIRCULATIONAHA.116.021612. Epub 2016 Apr 22.
  5. Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM,et al. COAPT Investigators.Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318. doi: 10.1056/NEJMoa1806640. Epub 2018 Sep 23.
  6. Truong QA, Rinehart S, Abbara S, Achenbach S, Berman DS, Bullock-Palmer R,et al. SCCT Women’s Committee.Coronary computed tomographic imaging in women: An expert consensus statement from the Society of Cardiovascular Computed Tomography. J Cardiovasc Comput Tomogr. 2018 Nov – Dec;12(6):451-466. doi: 10.1016/j.jcct.2018.10.019. Epub 2018 Oct 23.
  7. Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, et al. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2017 Apr;30(4):303-371. doi: 10.1016/j.echo.2017.01.007. Epub 2017 Mar 14.
  8. Weng Z, Yao J, Chan RH, He J, Yang X, Zhou Y, He Y.Prognostic Value of LGE-CMR in HCM: A Meta-Analysis. JACC Cardiovasc Imaging. 2016 Dec;9(12):1392-1402. doi: 10.1016/j.jcmg.2016.02.031. Epub 2016 Jul 20. Review.

 

 

hidden

The Unexpected Benefits of Extending Your Training

During my general cardiology fellowship, I developed a special interest in the care of patients with inherited cardiovascular disease. By virtue of the robust clinical activity of my division’s advanced heart failure and electrophysiology programs, I was exposed to clinical dilemmas like risk stratification in hypertrophic cardiomyopathy, primary prevention of sudden cardiac death in lamin A/C cardiomyopathy, and timing of heart transplantation for Danon disease early in my training. Refreshing my knowledge of clinical genetics alone was overwhelming, and I realized that while the rapid growth in genomic technologies was transforming our understanding of inherited cardiovascular disease, frontline clinicians were lagging behind in applying this knowledge to disease prevention and clinical care. To cultivate my interests further and learn to bridge this gap, I joined my institution’s new National Human Genome Research Institute (NHGRI)-supported postdoctoral training program in genomic medicine, a program created to prepare the next generation of physicians and scientists to implement genomic approaches to improve healthcare.

For M.D./D.O. trainees who have spent six consecutive years entrenched in clinical residency and fellowship programs, the idea of extending training by two years, re-entering the world of formal coursework and letter grades, and learning new skills to perform complex and unfamiliar research is more than enough to deter one from pursuing this career development track. However, participating in this program has afforded me many unexpected benefits outside the bounds of my clinical and research training:

  • Caring for patients with a new type of multidisciplinary team:
    • During my clinical training, my idea of a multidisciplinary care team was mostly grounded in my inpatient experience. While cooperating toward the same goal, physicians, nurses, advanced practice providers, therapists, nutritionists, pharmacists, social and case management workers often performed their roles asynchronously with little collaboration outside of the prescribed morning rounds. In contrast, my experience in our inherited cardiovascular disease clinic introduced me to a new paradigm essential to caring for patients and families with genetic disorders. I have been fortunate to learn about variant adjudication, pre-test and post-test counseling, cascade screening, and much more from our tremendous genetic counselors who are integral in the outpatient evaluations of our probands.
    • Though the initial years of my practice have been focused in adult medicine, I have learned about the importance of tracking variant segregation in families and of comprehensive transitions of care through our joint familial cardiomyopathy and arrhythmia programs, partnerships with our neighboring pediatric hospital.
    • Finally, I have witnessed the potential of real time bedside-to-bench-to-bedside research collaborations as shown by my mentors in their recent report of a clinical incorporation of rapid functional annotation of cardiomyopathy gene variants.1
  • Developing and sharing expertise:
    • In leading my fellowship’s didactic education curriculum as Chief Fellow, I took advantage of opportunities to share my new knowledge and skills with other fellows and residents. For our “fresh case” presentations, I often chose to present perplexing cases of cardiomyopathy to reinforce teaching points regarding the workup of genetic cardiomyopathies and the importance of taking a minimum three-generation family history.
    • After completing the Examination of Special Competence in Adult Echocardiography, I led a fellow teaching conference on echocardiography in hypertrophic cardiomyopathy. I also joined our internal medicine residents for a clinicopathologic conference as an expert discussant, a position usually reserved for faculty but generously offered to me given my interest in cardiovascular genetics and enthusiasm for teaching.
    • Pursuing these opportunities to develop and share my expertise has helped me solidify my own knowledge in the field, develop my oral and written communication skills, and grow as a peer mentor.
  • Meeting physicians and scientists outside of cardiovascular medicine:
    • The world often feels quite small while training within a medical specialty, but through my postdoctoral program, I have been exposed to physicians, scientists, and trainees in many disciplines outside of cardiovascular medicine. I heard diverse perspectives in my bioinformatics, biostatistics, and bioethics courses that have encouraged me develop my own independent opinions about my fields of interest. Multidisciplinary forums like genetics journal clubs, genetic rounds, and campus retreats have helped me contextualize the practice of genomic medicine.

 

 

My time in the postdoctoral program has shown me that these unexpected benefits of training are highly valuable to a trainee’s success. Through the genomic medicine postdoctoral program, the NHGRI “hopes to bring cross-training opportunities to individuals at different career levels and to support the training of investigators working in both basic genome science and genomic medicine” as it recognizes that this “is essential to realizing the full potential of genomics.”2

 

References:

  1. Lv W, Qiao L, Petrenko N, Li W, Owens AT, McDermott-Roe C, Musunuru K. Functional Annotation of TNNT2 Variants of Uncertain Significance With Genome-Edited Cardiomyocytes. Circulation. 2018;138(24):2852-2854.
  2. Green, Eric D. “NHGRI’s Research Training and Career Development: Genome Science to Genomic Medicine.” National Human Genome Research Institute. 3 Sept. 2014. https://www.genome.gov/27557674/may-5-nhgris-research-training-and-career-development-genome-science-to-genomic-medicine/

 

hidden

Late Breaking Science Trial: ORBITA Debate at Scientific Sessions 2018

“Life is like riding a bicycle. To keep your balance you must keep moving.” -Albert Einstein.

There may scarcely be any other sphere of medicine than interventional cardiology where the quote is more applicable. In 2017, the paradigm shifting ‘Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina’ – ORBITA  trial was presented and published.The results of this trial indicated that among patients with stable angina, percutaneous coronary intervention/PCI does not result in greater improvements in exercise times or anginal frequency compared with a sham/placebo procedure. This was despite the presence of anatomically and functionally significant stenoses. PCI did however resolve ischemia more effectively, as ascertained by follow-up stress.

This was clearly a landmark trial, but several issues were put forward as limiting factors. The trial was well conducted, with careful assessments of ischemia pre- and post-procedure, and appropriate use of antianginal medications-which unfortunately has been hard to replicate outside of the controlled setting of a trial, in the tribulations of real-world medical practice. Although powered for exercise treadmill-based endpoints, the trial has been noted to be too small to address a question of clinical benefits with PCI. Moreover, changes in Duke treadmill score and exercise time were both numerically higher in the PCI arm, and it is unknown if a larger sample size would have detected more modest improvements in exercise capacity.

The controversies and ‘buzz’ had prompted me to follow the data as a early career interventionist-and I cued in keenly for the short debate session on the same at the Annual Scientific Sessions of the American Heart Association 2018 (#AHA18) .Dr. Brahmajee Nallamothu, Editor of the Circulation: Quality and Outcomes and a Professor of Medicine at the University of Michigan- speaking in favor (PRO) of the findings from the ORBITA trial mentioned that while the myth that percutaneous coronary intervention’s prolong the life has long been debunked, a commonly held notion, and indeed one of the main reasons for performing PCI was to improve the quality of life in patients with significant coronary artery disease and symptoms. And ORBITA actually indicated that in a relatively healthy patient population, in a carefully conducted placebo controlled trial, the postulated benefits imparted with PCI were likely minimal. He went on to note that the trial was representative of a “real world” population of middle-aged patients with symptomatic coronary artery disease and  also referred to images from the original Lancet publication which indicated that the lesions that were treated appeared quite significant indeed. He concluded that in spite of  ongoing debates, results from ORBITA changed the way he discussed planned coronary intervention with his patients where he has changed his practice by incorporating a more tempered discussion on anticipated benefits with PCI, and has had greater conviction in advocating for more aggressive “medical” therapy.

Dr. Jay Giri from the University of Pennsylvania next took the stand in presenting the antagonistic (CON) version of the debate. Vying away from the anticipated track of discussing largely well publicized limitations of ORBITA, Dr. Giri took an innovative approach in going back to the fundamentals of the expected benefits from PCI. He presented data from recent studies which showed that PCI did reduce symptoms in patients with significant ischemia to a greater extent than optimal medical therapy alone. He also pointed to the fact that PCI reduced ischemia as well, and based on current understanding may mean favorably impacting future risk of subsequent adverse cardiac events including spontaneous myocardial infarctions (although that hypothesis is under evaluation with the on going ISCHEMIA trial). He honed in on the fact that the results from ORBITA had been sensationalized in both directions by ardent proponents and the media alike, while the “reality” was probably in between. With ongoing sub group analyses from the ORBITA trial itself, as well as follow-up studies being conducted, this is a rapidly evolving arena- and trainees /early career interventionists would do well in keeping themselves abreast of the nuances of the evolving data.

 

hidden

Clinical Significance of Sigmoid Shaped Interventricular Septum

A sigmoid-shaped interventricular septum (SIS) is generally considered a normal part of the aging process and is of little clinical significance. However, certain patients with SIS may experience clinical symptoms, such as dyspnea upon effort and different types of cardiac arrhythmias. SIS is frequently observed on transthoracic echocardiography (TTE) and in cardiac magnetic resonance (MR) imaging modality in daily clinical practice. However, nothing usually occurs in subjects with SIS, and the clinical significance of the presence of SIS is unclear.

The precise mechanisms leading to isolated SIS have yet to be determined, but plausible reasons exist as to why the basal septum might be uniquely susceptible to hypertrophy. For example, Laplace’s law states that the larger a vessel’s radius, the larger the wall tension required to withstand internal fluid pressures. Because the longitudinal fibers of the basal septum have some of the largest radii in the human heart, they would be expected to experience the greatest inward component of wall stress. This is compounded by the fact that the basal septum is the last part of the ventricle to be electrically activated, so contractions from other myocardial segments further increase its wall stress (Fig. 1). Moreover, the additional load created by pressure from the right ventricle exerts additional stress on the septum. Therefore, it is conceivable that the basal septum hypertrophies earlier than other LV regions in response to increased afterload as it already operates under higher loading conditions.

Clinical Significance of Sigmoid Shaped Interventricular Septum

Prospective studies suggest that up to 20% of cardiovascular cohorts may have isolated SIS. Some researchers have reported that the cause of SIS may be aging or arteriosclerosis. This may involve a change in the spatial relationship between ascending aorta (AA) and left ventricle (LV) due to elongation or tortuosity of arteriosclerotic AA. An alternative hypothesis suggests that SIS may be a form of cardiomyopathy. However, there is no evidence to support such a hypothesis due to the limited capabilities of traditional TTE. Use of other diagnostic approaches like CMR may be needed where characteristics of LV myocardium and the spatial relationship between AA and LV and degree of arteriosclerosis of AA can be evaluated simultaneously.

It is known that LV hypertrophy with different remodeling patterns is one of the major cardiac manifestations of hypertensive heart disease, and echocardiographic LV hypertrophy could be detected in 20-40% of patients with arterial hypertension. However, there are often no specific echocardiographic features for hypertensive patients at the early stage of disease. Previous echocardiographic studies have described asymmetric septal hypertrophy with a localized septal thickening at the basal-mid portion in patients with hypertrophic cardiomyopathy or aortic valve stenosis.

Basal-septal hypertrophy may also occur in a subset of older normal subjects, with normal wall thickness (WT) elsewhere, and is considered to be an age-related anatomic variant. This morphologic echocardiographic sign is termed as septal bulge (SB), sigmoid septum, or discrete upper septal thickening or knuckle. A large community-based population study reported that SB was documented frequently in elderly individuals with higher systolic blood pressure (BP). It was shown that the overall prevalence of SB was 1.5% and was markedly higher (18%) in the eighth decades of life.

Although pathologic and echocardiographic observations have indicated that SB is a structural response in hypertensive patients, the nature and significance of the SB in subclinical arterial hypertension was never investigated. In addition, despite the fact that BP can be easily measured, AH sometimes cannot be diagnosed due to the underreported BP reading in the casual or self-measured BP measurement. BP measurement with appropriate tools is essential to diagnosing AH early as well as to guiding AH management. It has been shown that, besides resting BP measurement in the office, arterial hypertension could be clinically diagnosed by 24-hour ambulatory BP monitoring (ABPM) as well as exercise stress test in some resting normotensive individuals.

Focal hypertrophy of the basal inter-ventricular septum can be seen in up to 20% of cardiac patients without HCM, being more prevalent in the elderly and hypertensives. While it’s anatomical location plausibly renders it more susceptible to hypertrophy, evidence suggests that the basal septum enlarges mainly due to pressure overload from hypertension. This discrete upper septal hypertrophy is associated with exertional LVOT obstruction and SOB, and appears symptomatically amenable to β -blockade. While diastolic dysfunction likely also contributes to symptoms in this condition, the data to date are equivocal. Focused analyses conducted using a consensus definition of SB, in patients undergoing simultaneous assessment of myocardial systolic and diastolic performance during physiological exercise, are needed to further understand the clinical relevance of this entity.

 

Fawaz Alenezi Headshot

Dr. Fawaz Abdulaziz M Alenezi is a Clinical Imaging Fellow at the Duke University Health Systems. He conducts medical research on the derivation and validation of novel echocardiographic approaches to myocardial deformation and a new echocardiographic technique which assists patients with heart ventricular function.

hidden

Strain Echocardiography: Values And Limitations – My Experience

“If echocardiographers are to stand still, depend on standard 2D echo imaging using equipment produced a decade ago and not upgraded since, perform ‘‘ejectionfractionograms’’, focus primarily on the left ventricle and simply ‘‘eyeball’’ the other chambers, and avoid new methods such as strain imaging and contrast echo because they are perceived as ‘‘a waste of time’’, then I fear that echocardiography will be passed by. As the dinosaurs illustrated, we need to adapt and continue to evolve, or face the consequences”.
Alan Pearlman- JASE editor, 2010

My research experience focused on heart failure and I conducted medical research on the derivation and validation of novel echocardiographic approaches to myocardial deformation. I have been heavily involved with all projects using strain echocardiography at Duke University (~ 40 projects over the last 5 years). My research has focused on 1) using echocardiographic methods to understand cardiac diseases through in depth pheno-typing, and 2) Left and right atrium strain. I have completed > 10,000 speckle tracking strain measurements analysis on different cardiac diseases and on different cardiac chambers.

Speckle Tracking Strain: Speckle tracking strain imaging has been around for quite a while and we celebrated the first decade 3 years ago, whereas the technique described in 2004 (Leitman M-JASE) and clinical applications appeared around 2005 (Notomi Y- JACC). Since then, the interest has risen dramatically and so far we have > 5000 publications on this topic. Left ventricular (LV) ejection fraction (LVEF), the most widely used measure of cardiac function, has important limitations including low sensitivity for incident HF, technique-related variability and does not directly assess LV contractility. Global longitudinal strain (GLS) is the most studied among strain parameters and its prognostic value has been demonstrated in several clinical scenarios. GLS was widely adapted by cardio-oncology and some studies showed that less negative GLS values at completion of chemotherapy predicted future LV dysfunction, despite normal LVEF. GLS played a vital role in the screening, diagnosis, and management of hypertrophic cardiomyopathy, amyloidosis, valvular heart disease, heart failure and many other diseases where the reduction on LVEF may be a late phenomenon or less sensitive.

Inter-Vendor Variety: GLS inter-Vendor variety has dramatically dropped over a short period of time. However, still if we look at the same images with different software vendors, we may have different values. This difference is due to several factors: 1) Image quality and acquisition; 2) Software used; 3) Where to measure (endocardial, myocardial, median); 4) Post-processing of data; 5) Patients age, gender variabilities and loading conditions. Recent study by (Farsalinos KE- JASE, 2015) showed that the mean values of GLS between different software vendors was almost 3.6%. I still think this is a big difference, however the good news from this study is that the reproducibility of GLS measurement seemed to be very good and better compared to routinely used LVEF. The study also showed that GLS has much less variation than other traditional echo parameters (E/A, wall thickness, LVEDD, EF, and E’).

Regional Strain: With regard to regional (segmental) function, we now have, for the first time, the possibility to measure regional myocardial function. However, I think this is more challenging than GLS, and there is still progress to be made. The challenges become because we have only one segment to work with, and less data to average. Tracking quality becomes more important, regional artifacts matters more, definition of sample position more relevant, and more importantly, we cannot simply measure peak values anymore. For regional analysis, the strain curve shape (not peak values, because peak values can be the same), become critical. Regional strain measurements have much higher variability among vendors when compared with GLS. Furthermore, I have notice a big difference when I measuring the normal segment and the abnormal (scar) segment.

Strain Patterns: Specific strain patterns, such as that attributed to cardiac amyloid, I believe the severity of the disease matter more than the etiology. I think some of chronic global heart diseases states such as hypertension, aortic stenosis, heart failure with preserved EF, etc. share similar strain patterns and the pattern depends not on the etiology, but on the severity of disease states. For example, in more severe (late stage) aortic stenosis, or hypertension, I have notice similar strain patterns that has been described in cardiac amyloid, that affect mainly the basal/med segments and spares the apex. The LV apex is comprised mainly of circumferential muscle fibers, that are facing different hemodynamics load (BP) or may be histologically different from the longitudinal muscle fibers (basal/ med). On the other hand, do these chronic diseases also have accumulation of proteins similar to amyloid and not necessarily represent a complete picture of cardiac amyloid. Still an area of research!

Normal Values: What is the reference values? is another common question. Personally, I think no normal values could be given and each echo-lab should build up their normative values according to the local data, software vendor used, image acquisition, experience and the echo machine setup. Much remains to be done on improving the software, acquisition layered strain, and updating the myocardial function documents. For this discussion, I focused on the 2D LV GLS, though there is also promising research on the left atrium and right heart, and right atrium strain which have traditionally been hard to characterize.

In summary, I think GLS is ready for clinical practice. Its robust, reproducible and has been shown to add unique data that can guide diagnosis and management. I recommend GLS as a valuable complement to traditional function parameters. Further studies are needed to standardize vendors, recognizing specific strain patterns and to determine if there are age, gender variabilities or loading conditions difference.

Fawaz Alenezi Headshot
Dr. Fawaz Abdulaziz M Alenezi is a post-doctorate associate at the Duke University Health Systems. He conducts medical research on the derivation and validation of novel echocardiographic approaches to myocardial deformation and a new echocardiographic technique which assists patients with heart ventricular function.