Myocardial Diseases (ABIM Review)

So picture this. You're evaluating an 80 year old man in the clinic. Okay. He's presenting with a new onset heart failure with preserved ejection fraction. Right. HFPEF. Exactly. And as you dig into his chart, you notice a surgical history of bilateral carpal tunnel releases a few years ago. Oh, that's a huge clue right there. It really is. Yeah. And maybe, um, maybe some lumbar spinal stenosis that's been bothering him too. Yep. Then you look at his ECG, given his really thick heart walls on the echo, you know, you'd expect massive voltages. But the ECG is surprisingly low voltage. It just doesn't match the echo at all. Right. It doesn't match. So what is the diagnosis? And perhaps more importantly for his survival, what, uh, revolutionary new medications could fundamentally change his prognosis? That is the big question. Welcome to the A-Bim series on evidence at the bedside. I'm Dr. Taylor. And I'm Dr. Griffin. Welcome back everyone. Today our mission is to transform the latest literature on myocardial diseases into, um, high yield actionable knowledge. Yes. We're structuring this episode specifically for passing the A-Bim boards and crucially for your day to day bedside management. Exactly. We're going to connect the dots between conditions that cause thick walls and stiff ventricles. So we're moving from the really hypercontractile, highly dynamic world of hypertrophic cardiomyopathy. H-C-M-Y. Right. Into the deceptive, infiltrative diseases like cardiac amyloidosis. And from there we'll tackle the diagnostic hemodynamics of restrictive cardiomyopathy versus constrictive pericarditis, which is always a tough one on the wards. It really is. And finally, we'll finish up with a look at cardiac masses. We are taking the recent guidelines and the established evidence and distilling it down to exactly what you need to know. And we're explaining the why behind the wards. So you know, you never have to memorize blindly again. So let's get right into the frequently tested board concepts. I think the best way to anchor this is with a classic board scenario. Okay. Lead on me. You're presented with a young patient, maybe a high school basketball player or a young professional, who comes in with unexplained disney on exertion. Or worse, the vignette describes an episode of syncopy right in the middle of a sprint. Exactly. This is the textbook setup for hypertrophic cardiomyopathy, H-C-M. To really understand how to answer the questions that follow and how to keep this patient safe in real life, we need to master the diagnostic reasoning. We really do. We have to break down the pathophysiology, starting with what the evidence describes as the eject upstrictly triad. The eject upstrictly triad. I mean, it's such a perfect mechanical description. It really paints a picture. It does. Let's unpack that because it's the foundation for literally everything else. Yeah. And you have H-C-M, you have asymmetric left ventricular hypertrophy. The myocardium is diseased at the sarcomere level, but macroscopically, the interventricular septum is disproportionately thick. It's bulging right into the left ventricular outflow track. The LVOT, exactly. And that physical bulge sets up a, well, a hemodynamic disaster. It really does. I always explain this to the residents by comparing it to a narrow hallway in a wind storm. Oh, that's a good analogy. Yeah. During ventricular cystal, as the heart starts to forcefully eject blood, the blood has to squeeze through that narrow outflow track. And according to the Bernoulli principle, fluid dynamics. Exactly. As fluid moves through a narrowed space, its velocity increases and the lateral pressure drops. It creates a suction effect, a drag force. And this high velocity jet physically pulls the anterior leaflet of the mitral valve away from where it's supposed to be. It drags it right toward that hypertrophied septum, which is what we call systolic anterior motion or SAM of the mitral valve. That's the eject leading directly to the obstruct part of the triad. Right. The SAM of the mitral valve physically blocks the left ventricular outflow track in early to mid-sisterly. The valve leaflet literally slaps against the septum, creating a dynamic mechanical obstruction to forward blood flow. But then comes the final piece of the triad, which is the leak. Because if the anterior mitral leaflet is being sucked into the outflow track, it's obviously not doing its actual job. Which is sealing the left atrium. Exactly. The mitral leaflets don't cope properly. So simultaneously with the outflow obstruction, you get a posteriorly directed jet of mitral regurgitation. Eject obstruct, leak, and it all happens in milliseconds. It's incredible. And you'll see the consequences of this abnormal anatomy on your non-invasive testing. Some writers love to test your ability to recognize the electrical signature of this disease. They will hand you an ECG. Oh, they definitely will. For the classic apical variant of HCM, you're going to see absolute massive QRS voltages. I mean, the QRS complexes will literally overlap with the leads above and below them on the paper. It reflects that extreme ventricular mass. But you'll also see deep, giant, symmetric T-wave inversions. Particularly in the Procordial Leads, V2 through V5. And those repolarization abnormalities can look incredibly alarming. If you're a tired intern in the ED, your first instinct might be that this patient is having a massive anterior stemmy. Or severe schemia. But in the specific context, combined with the extreme voltage, it's the electrical hallmark of profound apical hypertrophy. They're called dagger Q-wave sometimes, particularly in the inferior and lateral leads, because the septal depolarization is just so massive. Right. And when you move from the ECG to the echocardiogram, the diagnostic criteria become very rigid. They do. The recent guidelines define HCM as a maximal left ventricular wall thickness of 15 millimeters or greater. In any region of the left ventricle. Exactly. And crucially, this has to be in the absence of another loading condition that could explain the thickness. Like longstanding severe hypertension. Or critical aortic stenosis. But there's a really important caveat here that you have to look out for in the vignettes. That's that. If the patient has a first degree relative with established HCM, or if they have a known positive genetic mutation for the disease, that diagnostic threshold on the echo actually drops to 13 millimeters. Oh, right. Because the pretest probability is higher, so the threshold for diagnosis is lower. Exactly. That's a great point for the boards. But let's talk about where clinical reality pushes back against simple definitions. Okay. What do you do when you have a patient with classic symptoms, say, exesional dizziness and chest tightness? Yeah. And their echocardiogram shows that asymmetrical septal hypertrophy, but their resting left ventricular outflow tract gradient is only, say, 30 millimeters of mercury. Well, by definition, severe obstruction requires a gradient of 50 or more. Right. Do you just label them as having non-obstructive disease and assume their symptoms are from something else? Oh, absolutely not. And this is a massive pitfall that the boards will test you on. Yes, it is. You cannot rely solely on resting hemodynamics when you're evaluating HCM. The literature tells us that up to 40% of patients with HCM will have a left ventricular outflow tract obstruction only when provoked. If you don't actively look for the obstruction, you're going to miss it entirely. Precisely. The guidelines mandate that if the resting gradient is less than 50 millimeters of mercury, you must use provocative maneuvers during the echocardiogram. Like in the clinic, you have them perform a Vellsolva maneuver while the synographer is measuring the gradient. Or even better, you put them on a treadmill and perform an exercise stress echo. You're deliberately trying to alter the loading conditions, right? Yes. Increasing contractility and heart rate while decreasing venous return. To see if you can unmask that dynamic obstruction. Okay. So once we've established the diagnosis of obstructive HCM, whether at rest or with provocation, we have to navigate the management algorithms. The boards will undoubtedly test you on the stepwise progression of medical therapy. Absolutely. First line therapy, unequivocally relies on non-veso-dialating beta blockers. Minoprolol is the classic high yield choice here. Let's explain why that works because if you understand the why, you don't have to memorize it. Okay. So we use beta blockers primarily to decrease the heart rate. A slower heart rate lengthens diastole. And why do we care about diastole? Because this left ventricle is thick and stiff, it takes much longer to fill. By lengthening the filling time, we allow a larger end diastolic volume to accumulate. That larger volume of blood physically distends the left ventricle. It stretches the chamber, which physically pulls the mitral valve apparatus further away from that bulging septum. A wider outflow tract means a lower pressure gradient. Plus, the negative inattropid effect of the beta blocker reduces that initial forceful ejection velocity. Decreasing the drag forces that cause SAM in the first place, it makes perfect physiological sense. It does. But what if beta blockers are contraindicated? Say the vignette describes a patient with severe uncontrolled reactive airway disease. Or they just practically can't tolerate the profound fatigue of a high dose beta blocker. Right. The second line option is a non-dihydropyretine calcium channel blocker. The rapamil or diltiasm. They provide a similar negative chronotropic and negative inotropic effect. That's true, but honestly, the exam writers are far more interested in testing what you should avoid in these patients. It's almost more important to know the absolute contraindications. You must actively avoid vasodilating beta blockers. Yes. This is a critical pitfall, and I see residents get tripped up on this all the time. You cannot use carvitalol, libetolol, or nabivolol in obstructive HCM. Even though they are beta blockers, they're alpha blocking or direct vasodilating properties make them dangerous. Why? Because the vasodilation decreases systemic vascular resistance. It drops the afterlook. right. When you drop the afterload, there's less resistance pushing back against the heart, so the left ventricle empties much more rapidly and completely. The chamber size becomes significantly smaller during system. And a smaller emptier chamber brings the mitral valve and the hypertrophied septum much closer together. It's the exact same physiologic logic for why you must strictly avoid nitrates and phosphodiesterase 5 inhibitors. Nitrates are profound venodilators. They pool blood in the venous system and absolutely tank the preload. A drop in preload means less venous return, less ventricular filling, a smaller chamber size, and a dramatically worse gradient. I've seen case reports of HEM patients given sublingual nitro in the ER for chest pain, who immediately dropped their pressure in code. Because they completely obstructed their outflow track. Exactly. Furthermore, you have to counsel these patients vigorously about avoiding dehydration. The hemed completion is the arch nemesis of the HCM patient. A dry, underfilled left ventricle is an obstructed left ventricle. Now, beyond managing the symptoms of obstruction, the single most important intervention in HCM is risk stratification for sudden cardiac death. SCD. This is the primary reason these patients die young, mostly from devastating ventricular arrhythmias like V-Fid. The guidelines provide a very clear objective list of major risk factors that justify the placement of an implantable cardiovirder defibrillator. ICD. Right. On the boards, if you see any one of these major risk factors buried in a vignette, the correct answer for the next step in management is referring for an ICD. Let's outline them explicitly. When I'm evaluating these patients, I'm mentally checking off a very specific high-stakes list. Number one, a history of sudden cardiac death in a first-degree relative who was 50 years older younger. Number two, massive left ventricular hypertrophy. It's highly defined as a wall thickness of 30 millimeters or greater. Number three, a history of one or more episodes of unexplained syncopy that is highly suspected to be a rhythmic in nature. Meaning they went down suddenly without a pro-drome. Exactly. Number four, the presence of a left ventricular apical aneurysm. And number five, an evolving reduction in systolic function, specifically an ejection fraction that drops below 50%. If any of those are present, primary prevention within ICD is indicated. But here's where it gets nuanced. What about the patients who fall into the gray zone? The indeterminate risk cases. Right. They don't quite meet the criteria for a massive 30 millimeter wall thickness. They haven't passed out, but their family history is a little murky. The literature has evolved significantly here, and this is a highly testable update. We now rely heavily on cardiac magnetic resonance imaging. Specifically looking at late-gadolinium enhancement or LGE. The physics behind this are fascinating. They really are. Gadolinium is a contrast agent that washes out of healthy, tightly packed, normal myocardium very quickly. But it gets trapped in areas where the extracellular space is expanded. And in the context of HCM, that interstitial expansion represents myocardial fibrosis. Necroscopic scar tissue. Right. And scar tissue is the perfect heterogeneous electrical substrate for re-entrant ventricular arrhythmius. And the evidence gives us a hard cut off now. The recent guidelines state that if you quantify that LGE on the MRI, and it involves 15% or more of the total left ventricular mass, that is a critical tiebreaker. Extensive LGE of 15% or greater is independently associated with an increased risk for ventricular arrhythmius. And it warrants strongly considering an ICD, even if the other classic major criteria are completely absent. Okay, let's connect some concepts here. We've been deep in the weeds of genetic thickening of the myocardium in HCM. The myocytes themselves are hypertrophied due to sarcomeric protein mutations. But I want to shift our focus to a completely different mechanism. Infiltrate of thickening. Let's talk about cardiac amyloidosis. This is a vital diagnostic algorithm to master. It's an absolute must know for both the boards and the wards. Picture this. You have a patient with progressive heart failure, and the echo shows a thick, sparkling myocardium. But their ECG shows strangely low voltages. What we call a voltage to mass mismatch. Exactly. Get a cardiac MRI, and it shows diffuse, subbendocardial, late-gadolineum enhancement. Looks like amyloid. So what is the very first mandatory step in the diagnostic pathway? The single most critical point in the entire amyloid diagnostic algorithm. And I cannot stress this enough is this. What is it? If imaging suggests amyloidosis, you must always without exception, check for monoclonal light chains first. You are hunting for al amyloidosis. Exactly. And what's this specific lab panel you're ordering? You order serum and urine immunofixation electrophoresis and a serum-free light chain assay. Do not just order in spepp or a UPAP. No, they're not sensitive enough. You need the immunofixation and the free light chains. You have to do this immediately because al amyloidosis, which is driven by a clonal plasma cell dysgrasia, is a hematologic emergency. The pathophysiology here is so aggressive. The light chains themselves circulating in the blood are profoundly cardiotoxic. Entirely independent of their physical deposition as amyloid fibros in the tissue. They cause direct oxidative stress and myocyte necrosis. If you delay the diagnosis of al amyloidosis by even a few weeks, the patient can spiral into rapidly progressive, completely irreversible cardiogenic shock. Only after you have definitively ruled out al amyloidosis by confirming that the light chain studies are completely normal, do you proceed to the next step? Which is looking for transtheratin or ATTR amyloidosis. And the literature has completely revolutionized how we do this over the last decade. We used to rely heavily on invasive endomyocardial biopsies. Now if the light chains are negative, the evidence firmly supports using a 99-meter technicium pyrophosphate or PYP bone scan. The PYP scan is such a brilliant repurposing of old technology. We're using a bone-seeking radiotreaser. For reasons we don't entirely understand at a molecular level, but it's likely related to a high concentration of calcium microcalcifications within the ATTR amyloid deposits this tracer binds intensely to ATTR amyloid in the heart. But crucially, it does not bind to al amyloid. So the clinical pathway is incredibly elegant. If you have a patient with a clinical picture of heart failure, an echo showing a thick ventricle, totally negative serum and urine light chains, and a strongly positive cardiac PYP scan. Meaning the radiotreaser uptake in the myocardium is equal to or greater than the uptake in the ribs. You have definitively diagnosed ATTR cardiac amyloidosis. You are done. No endomyocardial biopsy is required. It's a remarkable triumph of non-invasive diagnostics. It really is. Now let's move from these comprehensive algorithms to things you just need to commit to permanent memory. Let's move into the Musno pearls. These are the rapid fire high yield facts that the A-Bin loves to weave into physical exam vignettes. Let's go back to the bedside physical exam for HCM. We mentioned earlier how loading conditions alter the murmur. But let's give the listeners the permanent memory hook. The memory hook I drill into my residence is simply this. Squatting makes the heart bigger. Let's logic through the hemodynamics together. When a patient squads down or when they're lying supine on the exam table and you passively elevate their legs, two major physiologic shifts happen simultaneously. First, you compress the large venous beds in the legs and abdomen. Forcibly increasing venous return to the right heart which drives up your preload. Second, you kink and compress the arterial beds in the legs. Which increases your systemic vascular resistance or afterload. Right, and both of those changes, an increase in preload and an increase in afterload, work synergistically to physically descend the left ventricle. We fill it up and make it harder for it to empty. A distended, larger, fuller left ventricle pushes the mitral valve apparatus away from the hypertrophied septum. The alphloid tract literally widens the mechanical obstruction lessons. And therefore, the intensity of that harsh crescendo to crescendo systolic ejection murmur decreases. And the exact opposite happens when you shrink the heart. Like if you have the patient bare down and perform a strain phase balsalva maneuver. The massive increase in intra-thoracic pressure completely chokes off venous return from the venocava. Preload plummets. Or if they rapidly stand up from a squatting position. Blood instantly pools in the venous system of the legs due to gravity. Again, preload plummets. The left ventricle becomes critically underfilled and geometrically smaller. The mitral valve and the septum are brought right next to each other. The obstruction worsens significantly. And the murmur increases in intensity. It's a beautiful demonstration of dynamic anatomy. Another incredibly high yield physical exam pearl is evaluating the peripheral pulse, specifically feeling the carotid or radial pulse after a premature ventricular contraction or a PVC. This tests a classic physiological concept known as the Brachimbrow Bronwald Morro sign. Let's think about what normally happens after PVC. There's a compensatory pause before the next sinus beat. During that abnormally long pause, diastyl is extended. So the left ventricle fills with significantly more blood than usual. Preload goes way up. You would normally expect the next contraction to be much stronger. Due to the Frank Starling mechanism, which says that a stretched myocardial fiber contracts with greater force. Because of that forceful contraction, the peripheral pulse you feel with your finger should be stronger. And in fixed-valvular aortic stenosis, that is exactly what happens. The pulse pressure increases. But here's where the pathology of HCM flips the script. in the dynamic outflow of destruction of HCM, that increased force of contraction from the Frank Starling mechanism actually backfires spectacularly. The ventricle contracts so forcefully and with such high initial velocity that the drag forces that Venturi effect we talked about on the mitral valve are massively amplified. The same of the mitral valve happens earlier and much more severely insistal. Exactly. The outflow tract is choked off prematurely. Because the door slams shut right as the ventricle is trying to empty. The actual forward stroke volume that makes it out into the aorta is significantly reduced. So paradoxically when you're feeling the pulse after a PVC in an HCM patient, the peripheral pulse remains unchanged or it actually decreases an intensity. You get a weaker pulse despite a stronger contraction. It's an absolute masterclass in bedside physiology. Let's shift gears to another absolute must-know-purl, this one concerning arrhythmias. When we think about atrial fibrillation in a standard primary care clinic, we reflexively reach for the CHAT-TA2-DS2-VASC score to determine the need for anticoagulation. It's practically muscle memory at this point. But in hypertrophic cardiomyopathy, you must throw the CHAT-2-DS2-VASC score completely out the window. The stroke risk from atrial fibrillation in an HCM patient is intrinsically elevated. Entirely independent of their age, gender, hypertension, or other comorbidities. The physiological logic behind this rule is really important to grasp. A patient with HCM has a severely hypertrophied non-compliant stiff left ventricle. Their diastolic function, their ability to relax and passively accept blood is terrible. Because passive filling is so profoundly impaired, their overall cardiac output relies desperately on the active atrial kick at the very end of diastyl. That atrial kick can account for 30 to 40 percent of their ventricular filling. So when they go into atrial fibrillation, they lose that organized coordinated atrial contraction entirely. Ventricular filling plummet, cardiac output drops precipitously, and left atrial pressures skyrocket. That resultant severe left atrial dilation. You have a huge atrium with stagnant blood, a massive nitis for thrombus formation. Therefore, the guideline is absolute black and white. Everyone with HCM who develops atrial fibrillation gets systemically anti-quagulated. Regardless of their CHATDS2VASC score, a 25-year-old elite athlete with HCM and A-Fib gets anti-quagulated. And a literature strongly prefers direct oral anti-quagulance or DOACs as first-line therapy over war-friend. Now let's jump back to Emily Dosis for some high yield systemic clues. The board's rarely give you a pure isolated cardiac presentation. They're going to give you a systemic phenotype, and your job is to match the phenotype to the offending protein. Let's look at AL-Emily Dosis first. Because AL is a systemic disease of circulating light chains, the amylate fibral deposit literally everywhere in the body. The classic triad to look for in a vignette includes nephrodite-range proteinuria. Because the kidneys, specifically the glomeruli, are a prime target for light-chained deposition. Second is macrogloseo, which is a massively enlarged stiff tongue, with scalloped edges from pressing against the teeth. And third is periorbital purer, often called raccoon eyes. This happens because amyloid deposits in the delicate capillary walls of the skin make them extremely fragile. Leading to spontaneous bruising or bleeding with very minor trauma, like just rubbing their eyes. If you see heart failure, massive progenuria, and a big tongue, you are dealing with AL-Emily Dosis until proven otherwise. On the other hand, Transceratin or ATTR-A-Emily Dosis presents very differently. And you have to separate it into its two demographic forms. First is hereditary ATTR or H-ATTR. This is due to an inherited pathogenic variant in the TTR gene. A major demographic pearl here that the boards love is the Val-1-2-Ile variant. That's a crucial one. This specific mutation is found in approximately 3.4% of individuals of African descent in the United States. It's an incredibly important health disparity to recognize. It often presents with severe sensory and autonomic neuropathy, like orthostatic hypotension, or severe GI-dismatility accompanying the heart failure. And then you have wild type ATTR or WT-ATTR. We used to call this senile cardiac amyloidosis, but we've moved away from that term. This is an aging linked process where the normal, unmutated Transtheratin protein simply becomes unstable over time, dissociates into monomers, and misfolds. This overwhelmingly affects older men, typically between the ages of 65 and 95. The systemic clues for wild type are often orthopedic, which is fascinating. You'll see an old man with heart failure with preserved ejection fraction. Who has a history of bilateral carpal tunnel syndrome, often requiring surgical release, five to ten years before the cardiac symptoms ever appear? You will also see a history of lumbar spinal stenosis, or spontaneous biceps tendon rupture, the so-called pop-eye sign. The amyloid fibrils literally deposit in the flexor retinaculum of the wrist and the ligamentum flavum of the spine long before they accumulate enough in the heart to cause symptoms. Those clinical phenotypes are pure gold for exam day, but we need to talk about how exam writers aren't just looking to see if you know the facts. They're actively trying to deceive you. Let's transition into discussing common board traps. They love to set up clinical scenarios, specifically designed to lead you down the wrong path. To see if you can distinguish between a zebra and a horse painted with stripes. We can call this segment the deceptive heart. I love that. Trap number one in the deceptive heart is the classic athlete's heart versus HGM dilemma. The vignette will paint a picture of a highly conditioned athlete, say, a 22-year-old competitive triathlete or a division I roar. Who is found to have left ventricular hypertrophy on a routine screening echo? The trap is to assume that because they're an elite endurance athlete, a thick heart is just a normal physiologic adaptation to intense training. You brush it off as athlete's heart and clear them to race. But if you do that in real life and it's actually HGM, that athlete could suffer sudden cardiac death on the field. The boards want you to know exactly how to differentiate the two non-invasively, and it comes down to geometry and function. An athlete's heart is primarily a volume-loaded state. They're moving massive amounts of blood. So they will develop eccentric hypertrophy. The left ventricular cavity size will be enlarged or dilated to accommodate those massive stroke volumes. And importantly, because the myocardium is healthy, their diastolic filling patterns on Doppler echo will be completely normal, or even supernormal, they relax beautifully. In stark contrast, the pathology of HGM is characterized by a small left ventricular cavity size. The hypertrophy is concentric or more commonly asymmetric, heavily favoring the septum without any compensatory dilation. And crucially, because the myocardium is genetically diseased, disorganized, and stiff, they will have objective evidence of diastolic dysfunction on the echo. Their relaxation is severely impaired. Now, if the echocardiographic indices are borderline, which happens often in the gray zone of 12 to 14 millimeters of thickness, and you're genuinely stuck, there's an ultimate diagnostic tiebreaker. You ask the athlete to undergo a brief period of total deconditioning. You have them stop training completely for three to six months. Physiologic athletes' heart is adaptive, it will begin to regress, and the wall thickness will measurably decrease. Pathologic HGM is a genetic disease. It will not regress one single millimeter. Trap number two is perhaps the most notorious differential diagnosis in all of cardiology, distinguishing restrictive cardiomyopathy from constrictive paracarditis. The trap is beautifully set because both conditions present virtually identically at the bedside. The patient has profound right-sided heart failure, massive acytes, severe peripheral edema, hepato-medally, and a hugely elevated jugular venous pressure. And importantly, on the echo, both conditions show preserved or near-normal left ventricular systolic function. The ejection fraction is fine. The boards will give you a patient with a history of radiation therapy for Hodgkin lymphoma 20 years ago. And they'll try to push you toward picking restrictive cardiomyopathy. Because we all know radiation causes myocardial fibrosis. But here's the catch. Radiation also obliterates and calcifies the paracardium. It causes both. So how do you solve the trap? You have to look at the underlying hemodynamics. The defining physiologic feature of constrictive paracarditis is ventricular interdependence. The heart is trapped inside a rigid, calcified, inelastic paracardial shell. The total volume of the heart is completely fixed. Let's walk through what happens when that patient takes a breath. Perfect. When you take a deep breath in, negative inter-thrastic pressure sucks blood into the chest, increasing venous return to the right heart. Because the total cardiac volume is fixed by that rigid shell, the right ventricle can only accommodate that extra blood by forcefully pushing the intraventricular septum to the left. It physically squashes the left ventricle, decreasing left-sided filling, and dropping the systemic blood pressure. The ventricles are literally competing for space. You can see this exaggerated septal shift, the septal balance on echocardiography, or prove it invasively with simultaneous right and left heart catheterization. But in restrictive cardiomyopathy, you do not have ventricular interdependence. The paracardium is normal. The problem is that both ventricles are just independently intrinsically stiff from amylide infiltration or fibrosis. They don't compete for space. They just both refuse to stretch. The exam riders will also give you laboratory and osculation clues to break the tie. The BMP or B-type name. and atrociously inaturated peptide is incredibly helpful here. In constriction, the problem is an external shell. The myocardium itself is relatively healthy, it's just squished. It literally cannot stretch enough to trigger the release of DMP from the myocytes. So a BMP of less than 100 pg per milliliter in a patient with slurred heart failure strongly points to constriction. Conversely, in restriction, the myocardium is heavily diseased, infiltrated, and under immense internal wall stress. Even though it's stiff, the cellular stress signals are firing constantly. The BMP is usually sky high, almost always greater than 400 pg per milliliter. And don't forget the osculation differential. Both conditions can produce an extra early diastolic sound as the ventricles rapidly fill and abruptly hit their elastic limit. In constrictive paracarditis, that abrupt halt of blood against the rigid, calcified paracardium creates a high frequency sharp sound called a paracardial knock. It's occurring just slightly earlier than a S3. In restrictive cardiomyopathy, the sudden deceleration of blood into a stiff, non-compliant, but non-calcified ventricle creates the classic, lower frequency sound of an S3 gallop. Trap number three is an update on older paradigms, and it catches a lot of clinicians off guard because it changed recently. We briefly touched on this, but it bears repeating as a specific board trap. The vignette gives you a classic presentation of wild-type ATTR amyloidosis. It's a 75-year-old gentleman with bilateral carpal tunnel, spinal stenosis, and a thick heart with low ECG voltage. The question asked for the most appropriate next step in diagnosis. One of the answer choices sitting right there at option B will be endomiocardial biopsy. That is the trap. Ten years ago that might have been the right answer. Today it is absolutely the wrong answer. The literature explicitly states that non-invasive testing is now the gold standard for diagnosing ATCR. The correct answer is to order serum and urine light chains to rule out AL. And if those are negative, proceed to the 99-meter Technician PYP scan. You only ever pick endomiocardial biopsy if the non-invasive test results are discordant like a positive PYP scan, but positive light chains, leaving you confused. Or if you strongly suspect AL amyloidosis, but you cannot find the amyloid deposits in a safer, extra cardiac biopsy like an abdominal fat pad aspirate or a bone marrow biopsy. The ability of the heart is an invasive last resort, not the initial next step. Their final board trap, trap number four, concerns cardiac tumors. The vignette will describe a patient who comes in with syncopy that is highly positional. For example, a 50-year-old woman who only feels light-headed or passes out when she bends forward to tie her shoes or when she lies on her left side. On physical exam, you hear a low frequency early diastolic sound and you might even hear a diastolic rumble at the apex. The trap is immediately assuming the patient has rheumatic mitral stenosis based on the diastolic rumble. The solution is recognizing the tumor plop. That extra sound is not the opening snap of a fibromatic rheumatic valve. It is a left atrial mixoma. These are the most common primary cardiac tumors, and they classically attach biostock to the façade ovalis on the interracial septum. Because they're on a stalk, they're highly mobile. Depending on the patient's position, the tumor can literally prolapse or drop right into the mitral valve or if it's during diastolic. Causing an abrupt transient severe mechanical obstruction. That sudden halt of the tumor mass as it hits the end of its stalk or slams into the mitral valve ring is the tumor plop. And the boards want you to be able to contrast the mixoma with other rarer cardiac tumors. If the vignette describes a tumor that looks like a sea anemone or a small front-like mass attached directly to the downstream side of the aortic or mitral valve leaflets, and the patient just had a cryptogenic stroke, you're looking at a pepillary fibroelostoma. These are notoriously highly embologenic. Pieces of them break off and go straight to the brain. Conversely, if the vignette describes a highly malignant, aggressive process, a patient presenting with rapid onset right-sided heart failure, a large recurrent, bloody paracardiol effusion, and imaging, showing a massive, poorly defined mass, invading the actual muscular wall of the right atrium. The diagnosis is an angiosarcoma. It is the most common primary malignant cardiac tumor, and unfortunately the prognosis is exceptionally dismal. So we've covered the diagnostic algorithms, the hemodynamics, the physiology, and we've navigated the board traps. Now let's drive this entire discussion right back to where it matters most. The bedside. Let's focus on key clinical pearls. How do these guidelines actually change your daily workflow on the wards or when you're sitting across from a patient in the clinic? Let's talk about the most paradigm-shifting therapies in HCM in decades. The cardiac myosin inhibitors, Mava Compton, and the newer agent, Efficompton. These drugs are truly revolutionary because for the first time, they aren't just treating the symptoms of HCM like beta blockers do. They are the first therapies to directly target the underlying molecular pathophysiology of the disease. As we discussed, the root problem in HCM is a mutated sarcomere that is fundamentally hypercontractile due to excessive unregulated cross bridging between actin and myosin filaments. Mava Compton and Efficompton specifically bind to cardiac myosin and physically decrease that actin myosin crossbridge formation. They essentially act as molecular breaks. They calm the hypercontractile heart down, promote relaxation, and significantly reduce the left ventricular outflow tract gradient. But here is the critical bedside application, and this is where the practicing internist really has to pay attention. The margin for error with these drugs is incredibly thin. If you push that molecular break too hard, you go from reversing hypercontractility to inducing profound, dangerous hypokontractility. You can plummet the patient's ejection fraction in a matter of weeks and throw a previously stable patient into acute severe systolic heart failure. Because of this severe risk, the FDA mandated a strict risk evaluation and mitigation strategy or REM-BASS program. You can't just write a prescription for Mava Compton, hand it to the patient and say, "I'll see you in six months." At the bedside, prescribing these drugs means committing to a rigorous, non-negotiable schedule of serial echocardiography. You have to check their ejection fraction before they start the drug, a month after they start, and periodically forever. If the ejection fraction drops below 50 percent at any point, the REMAS protocol dictates you have to hold the drug immediately. And the logistical headache doesn't stop there. Mava Compton is heavily metabolized by the liver via the cytochrome P450 system, specifically C-WR-P2C19 and C-Y-P3-A4. The potential for catastrophic drug interactions is immense. If you start a patient on a moderate C-Y-P inhibitor, like certain anti-fungals, fluoxetine, or even if they start drinking massive amounts of grapefruit juice, the metabolism of Mava Compton Holtz. The drug levels in the blood will spike exponentially. And the patient could go into cardiogenic shock from severe systolic dysfunction. You have to meticulously reconcile their medication list at every single visit. It's a high-reward, high-maintenance therapy. Let's move from the high-tech, outpatient pharmacology of HCM back to the gritty, daily reality of managing restrictive cardiomyopathy on the inpatient wards. I call this the "diuretic tightrope." And it's a trap I see residents fall into constantly. Patients with RCM, whether from advanced, amyloid infiltration or radiation fibrosis, have profoundly stiff, non-compliant ventricles. Their ventricular pressure volume compliance curve is practically a vertical line. This means they require remarkably high-filling pressures, a huge pre-load, just to stretch the ventricle enough to maintain a basic stroke volume and a sustainable cardiac output. And that's the ultimate clinical paradox. They require high pressures to survive and perfuse their organs, but those exact same high-pressures translate backward into the venous system, causing severe, debilitating congestive symptoms. They come in with massive excites, hepato-megely causing abdominal pain and weeping lower extremity edema. When they get admitted to your medicine service, your instinct and the patient's request is to diurease them aggressively with intravenous loop diuretics to relieve their suffering. That is exactly where the trap lies at the bedside. If you pull off even a slightly excessive amount of intravascular volume, you drop their central venous pressure, you drop their pre-load. Because their stiff ventricle cannot actively relax to suck blood in, a drop in venous pressure means the ventricle simply does not fill during diastole. Their cardiac output tanks instantly. The blood pressure drops, the kidneys lose perfusion, and they go into a cute kidney injury. I remember an intern vigorously diureasing an amyloid patient over the weekend to dry them out, and by Monday morning, the patient's creatinine had tripled and they were in a low output state. Treating an RCM patient on the wards requires an ultra-careful, hyper-vigilant titration of diuretics. You can't just order a furostmide 44V twice a day and walk away. You need rigorous daily weights, strict intake and output monitoring, and constant reassessment of their renal function, their lactate, and their perfusion status. You are constantly walking a razor-thin tightrope between drowning them in their own congestion and starving their vital organs of forward flow. Finally, let's discuss a very practical scenario that arises in the clinic all the time. A patient you've been managing is formally diagnosed with hypertrophic cardiomyompthy. The shock of the diagnosis settles, and their very first question to you will be, "Are my children going to get this? Should they be tested right now?" The guidelines provide a very specific evidence-based workflow for genetic screening. And as an internist, you must know how to navigate it in Council of Family. The golden rule of genetic testing in inheriting cardiomyopathies is this. You must all Always, always genetically test the index patient first. Do not send a broad genetic panel on the asymptomatic 10-year-old child. You test the person sitting in front of you with the established disease. If you identify a known pathogenic variant, say, specific mutation in the NYVPC3 gene in the index patient, that is incredibly powerful information. You can now use that specific genetic target to test the first degree relatives, the parents, siblings, and children. This is called cascade screening. If a family member tests negative for that specific familial mutation, they are definitively cleared. They do not have the gene, they will not get the disease, and they do not need lifelong cardiac screening. But, and this is a massive butt that trips up many clinicians. What happens if you test the index patient who has classic, eco-proven textbook HCM and their genetic test comes back totally negative? The commercial panel finds no known pathogenic variants. Does that mean their disease isn't genetic? No, not at all. It just means our current genetic technology isn't smart enough or comprehensive enough to find their specific private family mutation yet. The absence of an identified sarcomaric variant does not exclude familial HCM. And here is the vital clinical pearl. If the index patient is genotype negative, you cannot use genetic testing to screen or clear their family members. Because you don't know what gene to look for, a negative test in the child means absolutely nothing. Exactly. In this gene type negative scenario, all first degree relatives must undergo rigorous clinical screening. They need an ECG and an echocardiogram to look for the physical manifestation of the disease. For adult relatives, this must be repeated every three to five years. For children and adolescents whose hearts are actively growing and who are at a much higher risk for sudden phenotypic changes, they need an ECG and echo every one to two years until they reach adulthood. It's a massive lifelong commitment to longitudinal care that you have to explain to the family. We've covered an immense amount of ground today. Let's rapidly recap the absolute essentials, the high yield facts you need to have tattooed on the inside of your eyelids for the exam and the words. For HCM murmurs, remember the hemodynamic rules. Anything that makes the left ventricle bigger squatting, passive leg elevation decreases the obstruction and decreases the murmur. Anything that makes it smaller, vulsaulva, rapid standing worsens the obstruction and increases the murmur. If your HCM patient develops atrial fibrillation, you completely ignore the CAK2-DS2VN-ASC score and you start them on a DOAC immediately to prevent a catastrophic stroke. For cardiac amyladosis, remember the diagnostic pathway. If the MRI or echo suggests it, you strictly check serum and urine immunification in the free light chains first to rule out the hematologic emergency of AL amyloid. Only then do you use a PYP scan to definitively diagnose ATTR amyloid without an invasive biopsy. And finally, when differentiating restrictive cardiomyopathy from constrictive paracarditis, look for ventricular interdependence that's septal bounce in a low BMP in constriction versus a sky high BMP and an S3 gallopin restriction. Before we close, I want to leave you with a final thought to ponder, something that really highlights how rapidly our field is evolving. As our diagnostic tools improve, particularly as genetic sequencing and advanced imaging like PYP scans become cheaper and more ubiquitous, the lines between what we consider normal aging and what we define as disease are blurring rapidly. It's so true. Ten years ago, wild type ATTR was known as senile cardiac amyloidosis. It was viewed as an inevitable, untreatable part of simply getting old. And prevailing thought was, well, the heart gets stiff because you're 80. Now we recognize it as a specific, targetable, and treatable disease process with new therapies, like tathamitas that stabilize the protein and fundamentally alter the natural history of the condition. It begs a provocative question for all of us in internal medicine. How many other progressive dysfunctions, things we currently write off as the normal wear and tear of aging, are actually just undiagnosed, misfolded proteins, cellular derangements, or localized infiltrative processes waiting for us to develop a targeted therapy. That's exactly why we continually review the literature and practice evidence at the bedside. The science is always evolving, and our patients rely on us to evolve with it. We invite you to like, share, and subscribe to Evidence at the Bedside so you never miss an update. I'm Dr. Taylor. And I'm Dr. Griffin. Thank you for joining us for this A-BIM series. We'll see you next time.