By Dr. Saleem Toro
June 202 2024
Please watch this video. It raises some important ethical questions regarding definition of brain death.
Can the body stay alive entirely on life support and all ancillary treatment modalities if the brain ceases to function entirely, both cortex and brain stem? It has been shown that it can. Then, where does the life of a organism reside? In the brain or in the rest of the body including heart, lungs and kidneys.
Amin H. Karim MD June 21 2024
LITERATURE REVIEW
Hema Manvi Koneru, MBBS,
Rajiv Gandhi Institute of Medical Sciences, Telangana, India
Divyasri Koneru, MBBS,
Dr.Pinnamaneni Siddartha Institute of Medical Sciences and Research Foundation, Andhra Pradesh, India.
Amanpreet Kaur, MBBS,
Government Medical College, Patiala, Punjab, India.
Amin H. Karim MD
Baylor College of Medicine, Houston, Texas
Introduction
Heart failure (HF) is a prevalent and serious condition associated with substantial morbidity and mortality. Management strategies have evolved, with recent focus on sodium-glucose cotransporter 2 (SGLT2) inhibitors potentially offering novel therapeutic benefits.
SGLT2 Inhibitors in HF with Reduced Ejection Fraction (HFrEF)
Studies have demonstrated that dapagliflozin, an SGLT2 inhibitor, significantly reduces the risk of worsening HF or cardiovascular death in patients with HFrEF. (1,3) The DAPA-HF trial, a pivotal phase 3 study, enrolled patients with New York Heart Association (NYHA) class II-IV symptoms and ejection fractions ≤ 40%. Results showed a reduction in the primary outcome (composite of worsening HF or cardiovascular death) among those treated with dapagliflozin compared to placebo (HR 0.74, 95% CI 0.65-0.85). This benefit was observed regardless of diabetes status, highlighting potential glucose-independent mechanisms of action.
SGLT2 Inhibitors in HF with Mildly Reduced or Preserved Ejection Fraction
Emerging evidence suggests that dapagliflozin may also benefit patients with HF and preserved or mildly reduced ejection fraction (HFpEF and HFmrEF). (2) The DELIVER trial randomized patients with HF and ejection fractions > 40% to dapagliflozin or placebo. Results indicated a reduction in the composite of worsening HF or cardiovascular death with dapagliflozin (HR 0.82, 95% CI 0.73-0.92). Moreover, improvements in symptom burden were noted, supporting potential broad utility across HF phenotypes.
Mechanisms of Action
Beyond glycemic control, SGLT2 inhibitors like dapagliflozin may exert beneficial effects in HF through mechanisms including improved cardiac remodeling, reduced sodium retention, decrease plasma volume, and potential metabolic modulation. These mechanisms contribute to improved hemodynamics and reduced cardiovascular morbidity and mortality, as observed in clinical trials.
Contraindication
Safety and Tolerability
Safety profiles across trials indicate that dapagliflozin is generally well tolerated in HF patients, with adverse event rates comparable to placebo. Common side effects include volume depletion and renal dysfunction (Acute kidney injury due to dehydration), which are manageable with appropriate monitoring. Other severe side effects are euglycemic diabetic ketoacidosis, allergic reaction and genital infections (mostly fungal).
Clinical Implications and Future Directions
The efficacy of SGLT2 inhibitors in reducing HF-related events underscores their potential as adjunctive therapy in standard HF management. Future research should focus on optimizing patient selection, exploring combination therapies, and elucidating long-term benefits and risks in diverse patient populations.
Conclusion
SGLT2 inhibitors like dapagliflozin show great promise in improving outcomes for patients with heart failure. These medications not only reduce cardiovascular risks but also improve quality of life, highlighting their potential as essential elements of comprehensive heart failure treatment strategies.
References
Hema Manvi Koneru, MBBS
Rajiv Gandhi Institute of Medical Sciences, Telangana, India.
Amanpreet Kaur, MBBS
Government Medical College Patiala, India.
Divyasri Koneru, MBBS
Dr.Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, India
Amin H. Karim MD FACC,
Clinical assistant professor, Baylor College of Medicine, Houston, Texas.
A 74-year-old male presented with complaints of dizziness. His medical history includes hypertension, diabetes mellitus, mitral regurgitation, tricuspid regurgitation, and a transient ischemic attack five months prior. Additionally, he reported two episodes of memory lapses within the past year.
The patient denied experiencing orthopnea, paroxysmal nocturnal dyspnea, chest pain, smoking, shortness of breath, leg swelling, speech disturbances, disequilibrium, blurry vision, syncope, tinnitus, hearing loss, ataxia, numbness, tingling, pins, and needles in the arms or legs.
MEDICATIONS
Aspirin 81mg sustained-release oral tablet, once daily; atorvastatin calcium 80mg tablet, taken orally once daily; clopidogrel 75mg tablet, taken orally daily; dulaglutide 0.75mg/0.5ml subcutaneous pen injector, administered subcutaneously once weekly; gabapentin 300mg oral capsule, taken once daily; losartan 25mg tablet, taken orally once daily; metformin hydrochloride 750mg extended-release tablet, taken twice daily with meals; nitroglycerin 0.4 mg sublingual tablet, to be used when chest pain persists; and thiamine 100 mg oral tablet, taken once daily. These medications have been prescribed to effectively manage the patient’s medical conditions and symptoms.
The patient had a history of allergy to the contrast medium used for the radiological examination.
ELECTROCARDIOGRAM
NUCLEAR STRESS TEST
No occlusive disease.
Following a thorough workup and assessment of the patient’s clinical presentation, imaging studies, and diagnostic tests, a final diagnosis of subclavian steal syndrome was made. This condition is attributed to the underlying pathology of atherosclerosis which mainly affects the subclavian artery.
DEFINITION
It is characterized by the retrograde flow of blood in the vertebral artery, primarily resulting from significant stenosis or occlusion in the pre-vertebral subclavian artery resulting in cerebrovascular symptoms on the ipsilateral side of the occlusion.
§ During exertion, the subclavian artery steals blood from the vertebrobasilar artery circulation to supply the arm, which leads to vertebrobasilar insufficiency.
SUBCLAVIAN STEAL PHYSIOLOGY
EPIDEMIOLOGY
The prevalence of subclavian steal syndrome has not been well defined, although subclavian steal physiology has been reported in 1.3 to 2.6% of the general population of patients with extracranial atherosclerosis (1,2) as well as within subsets of those presenting with acute ischemic stroke (3)
Subclavian stenosis more commonly occurs on the left side (>75 percent), possibly due to more acute origin on the left subclavian artery resulting in accelerated atherosclerosis from increased turbulence. (4,5,6)
Neurovascular symptoms can be caused by vertebrobasilar ischemia of the brainstem or cerebellum
Atypical neurological presentations- there is also increasing recognition that patients with vertebrobasilar insufficiency can present with other types of symptoms not directly attributable to brainstem or cerebellar ischemia.
Although neurovascular symptoms associated with subclavian steal physiology occur in only a minority of patients, symptoms of vertebrobasilar ischemia demand critical evaluation (10,11)
When to suspect subclavian steal syndrome
PHYSICAL EXAMINATION
RADIOLOGICAL EXAMINATION
1. Duplex ultrasound
2. Transcranial doppler ultrasound
DIAGNOSIS
DIAGNOSTIC CRITERIA– the presence of subclavian steal physiology with demonstration of a subclavian artery stenosis/ occlusion proximal to the origin of the vertebral artery causing
The likelihood that the presence of subclavian steal physiology will lead to the subclavian steal syndrome increases as the brachial pressure differential between the two limbs becomes more pronounced, particularly >40mmhg (5)
These include all the potential causes of vertebrobasilar embolism due to atherosclerosis, hypertension, hypercoagulable states, tumors, tobacco smoking, trauma, and others
Management of patients with subclavian steal syndrome is individualized depending on the etiology, type, and severity of symptoms and their impact on quality of life
ATHEROSCLEROTIC SUBCLAVIAN STEAL SYNDROMEAPPROACH
For most patients with atherosclerosis as the etiology for subclavian steal syndrome, conservative management is the preferred initial therapy.
This case highlights the importance of a detailed evaluation of subclavian steal syndrome can be due to atherosclerosis or non-atherosclerotic causes like Takayasu arteritis, giant cell arteritis, arterial thoracic outlet syndrome, and other causes. In our case, it might be a subclavian steal syndrome secondary to atherosclerosis.
REFERENCES
KESTELOOT H, VANHOUTE O. REVERSED CIRCULATION THROUGH THE VERTEBRAL ARTERY. Acta Cardiol. 1963;18:285-99. PMID: 14045892.
Rodriguez-Lopez JA, Werner A, Martinez R, Torruella LJ, Ray LI, Diethrich EB. Stenting for atherosclerotic occlusive disease of the subclavian artery. Ann Vasc Surg. 1999 May;13(3):254-60. doi: 10.1007/s100169900254. PMID: 10347257.
Gutierrez GR, Mahrer P, Aharonian V, Mansukhani P, Bruss J. Prevalence of subclavian artery stenosis in patients with peripheral vascular disease. Angiology. 2001 Mar;52(3):189-94. doi: 10.1177/000331970105200305. PMID: 11269782.
Murumkar V, Jabeen S, Peer S, Ramalingaiah AH, Saini J. Ruptured vertebrobasilar junction aneurysm unmasking subclavian steal syndrome. Surg Neurol Int. 2020 Dec 4;11:419. doi: 10.25259/SNI_561_2020. PMID: 33365182; PMCID: PMC7749953.
Ahuja CK, Joshi M, Mohindra S, Khandelwal N. Vertebrobasilar Junction Aneurysm Associated with Subclavian Steal: Yet another Hemodynamic Cause for Aneurysm Development and Associated Challenges. Neurol India. 2020 May-Jun;68(3):708-709. doi: 10.4103/0028-3886.288981. PMID: 32643699.
Tonetti DA, Jankowitz BT. Subclavian Steal Flow-Related Aneurysm Formation. World Neurosurg. 2019 May;125:101-103. doi: 10.1016/j.wneu.2019.01.186. Epub 2019 Feb 8. PMID: 30743034.
From Accidents to Advancements in the Realm of Medications.
Mahmood Syed, MS4
American University School of Medicine
Amanpreet Kaur, MBBS
Government Medical College Patiala, India
Amin H. Karim MD FACC
Clinical Assistant Professor
Baylor College of Medicine, Houston, Texas.
“When you have acquired knowledge and experience, it is very pleasant to
break the rules and to be able to find something nobody has thought of.”
These were the words of renowned Bacteriologist, Andrew Fleming, who
discovered Penicillin widely used today.
There are drugs whose original discovery was intended for
specific indications. However, their side effects were so
useful that these medications were eventually repurposed as
treatments for other medical conditions. This phenomenon is
also known as “drug repurposing” or “serendipitous
discovery”. Here are some examples of such medications
widely used today:
The discovery of Minoxidil is a fascinating chapter in medicinal
advancements. It was initially created for the treatment of
Hypertension. However, during clinical studies, scientists discovered a
surprising adverse effect that caused hair growth in patients that were
taking this medication. This coincidental finding prompted more
research into Minoxidil’s potential as a male pattern baldness remedy.
Eventually, it was repurposed for this indication.
Viagra (Sildenafil) is another interesting medication that was
unintentionally found while being used in the treatment of Angina
Pectoris and Pulmonary Hypertension. An unanticipated side effect that
the researchers discovered during clinical trials was that many of the
male participants reported having better erectile function after taking this medication due to its vasodilatory effects. Therefore, it was
repurposed as a medication for men suffering from Erectile Dysfunction
(ED).
Bimatoprost was another medication that was initially discovered for the
treatment of Glaucoma, but researchers noted that it increased eyelash
length, thickness, and blackness in the patients who received these eye
drops for the treatment of Glaucoma. This led to its use for cosmetic
enhancement of eyelashes today.
Ozempic (Semaglutide) was originally discovered for the treatment of
Type 2 Diabetes Mellitus. This medication functioned as a GLP-1 agonist.
Researchers found that it caused significant weight reduction in addition
to controlling blood glucose levels. After further clinical trials, it was
approved as a medication for weight loss.
Gabapentin was initially discovered as a potential treatment for seizures
as it was structurally similar to the neurotransmitter GABA. After its
initial discovery, Gabapentin was subsequently found to have efficacy in
treating neuropathic pain in patients who were treated for seizures,
leading to its approval for this indication as well.
Finasteride was initially investigated for its potential use in the
treatment of Benign Prostatic Hyperplasia. While clinical trials were
ongoing to see the effectiveness of this medication for BPH, it was
observed that patients taking finasteride experienced hair growth as a
side effect. Eventually, it was repurposed for the treatment of hair loss.
Methotrexate, a potent inhibitor of Folate metabolism, was used for the
treatment of many cancers including Acute Lymphocytic Leukemia (ALL)
and Choriocarcinoma. It was discovered to be effective in treating
autoimmune conditions due to its ability to inhibit cell growth and
modulate immune responses. Today, it is used to treat conditions like
Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA).
The development of aspirin from a painkiller to a multi-indicated drug is
evidence regarding its healing characteristics. Initially, aspirin was found
to be useful for reducing fever and pain. However, it is now essential for
maintaining cardiovascular health, controlling inflammation, and even
preventing and reducing the incidence of cancer, particularly in the
setting of colon cancer. This extensive range of applications highlights
the significance of aspirin in modern medicine and
its ongoing importance over a century after it was
initially discovered.
There are other medications that produce treatment indications as a result of
their side effect. In the world of ever-evolving medicine and advancements in
medical research, there is no doubt there will be more discoveries of newer
medications as well as current medications with newer indications. The
medical field is expanding on a level never experienced before in humanity. As
new therapies become available, as well as more research being generated as
a result of clinical trials and controlled studies, we will see an even greater
advancement in medicine in the near future than we have ever seen before.
The only limitation that we have is the limitations we set on ourselves. In the
book, The Laws of Medicine, by Pulitzer Prize-winning author Siddhartha
Mukherjee, he says “ In medicine, mistakes are inevitable but learning from
them is essential.” Furthermore, if these mistakes lead to newer discoveries
and treatments in the realm of medicine, then mistakes might just be better
than getting it right the first time.
By Dr. Aftab Naz
It was 1981. I had finished my residency at Cook County Hospital Chicago 2 years ago & was struggling to find a private practice. Those days were rather difficult to establish a new pediatrics practice as most of the Family practice docs would take care of the kiddos. After working as part time attending physician at Cook county Hospital Chicago with moonlighting here & there, I decided to move to California. In fact a friend of mine Dr M Ashraf, who was already practicing Cardiology in Madera California, invited me to visit the town & take over a small practice which was for sale.
So 43 years ago June 1, 1981 I started my practice. It was slow going but steadily improving. One day an 11 month old girl Maria was brought it with fever & jaundice. Since Hepatitis A was common at that time in the area, I diagnosed her with it & advised routine dietary management. A week later she returned with ascites.
Her liver was failing, so I admitted her in the community hospital & initiated the workup. Her LFT,s were slightly abnormal, bilirubin was about 8 mg/dl & hemoglobin was about 10gram. All other tests were normal. Due to increasing ascites, I transferred to local Children hospital in Fresno
At the children hospital a GI fellow would come twice a month from UCSF San Francisco. He decided to transfer Maria to SFO as her ascites was worsening inspite of treatment with diuretics & whatever else they had.
At UCSF, a liver biopsy was done & found to have nonspecific inflammatory changes. In the next 3 weeks, her ascites got significantly worse. Parents were advised that she had liver failure & she was not going to make it . So they decided to bring her back home to Madera AMA as it was easier to transport a live person than a dead body.
MARIA IN MADERA
By this time about 2 months had passed & patient was really uncomfortable due to increased intra-abdominal pressure. She has persistent cough due to shortness of breath. She was brought back to my office for cough. I advised them that she needs relief of pressure from her abdomen. Parents did not want any heroic measures done as “ she is going to die anyway “. I advised them that “yes. But let her die in peace”.
I called FRESNO children hospital & UCSF & they both refused to take her in as she was terminal anyway. Our local Gastroenterologist & surgeon also had their hand up by saying they were not pediatrics specialists. I asked an old FP how to do an abdominal paracentesis & admitted her in my local hospital.
This was my FIRST & LAST abdominal tap of my life. I took out 700 CC fluid first day & another 300 CC. the next day. She was comfortable & was discharged home.
I saw her in my office a week later. Her abdominal girth was the same as at the time of discharge. A month later her abdominal girth was normal & she was an active happy toddler. At age 16 Maria had splenic infarction & had splenectomy done at our hospital. At age 18 she had her first child & after 3 children she moved out of town & got lost to follow up.
I had been a “PEER” for the family. They sent me so many patients. And my practice flourishes until now thank God. All I did was make her comfortable.
I informed the UCSF about the happy outcome and they asked me to send her back for further biopsy which I did not comply. They were not helpful when I needed them the most. Unfortunately I never thought of getting all the medical records & write it up for a journal. Now our hospital has been closed also. This story is all from my memory.
Aftab Naz–
GlobeMedic 