I. What every physician needs to know.
Hypertrophic cardiomyopathy is the most common genetic cardiac disease, and occurs when there is marked left ventricular hypertrophy in the absence of inciting factors, such as hypertension. It is caused by autosomal dominant mutations in one of 10 different genes coding for proteins needed to form the cardiac sarcomere, with more than 80% of these mutations occurring in the beta-myosin heavy chain, cardiac troponin T, and myosin-binding protein C. These mutations lead to a disorganized arrangement in cardiac myocytes resulting in hypertrophy. This hypertrophy leads to the complex pathophysiology characteristic of hypertrophic cardiomyopathy which includes left ventricular outflow tract obstruction, diastolic dysfunction, mitral regurgitation, myocardial ischemia, and arrhythmias.
As more information has been gathered about this disease process it has been found to be increasingly heterogenic in its phenotypic expression. A large proportion of patients with hypertrophic cardiomyopathy are asymptomatic and can anticipate a normal life expectancy. Left ventricular outflow tract obstruction is not always present as one third of patients have no obstruction either at rest or with provocation. It is important to distinguish between the obstructive and nonobstructive forms of this disease, however, as this will determine management. In truth, only a small subset of patients with this disease suffer from the more significant complications, which include symptomatic heart failure, atrial fibrillation, and sudden cardiac death due to ventricular tachyarrhythmias.
Along with disorganized and hypertrophied myocytes, this disease process manifests with abnormal intramural coronary arteries. They have thickened walls and are considered small vessels. This leads to a mismatch between cardiac muscle and perfusion leading to episodes of ischemia. This ischemia may be part of the driving force behind the arrhythmias seen in this disease process.
II. Diagnostic Confirmation: Are you sure your patient has hypertrophic cardiomyopathy?
The diagnosis of hypertrophic cardiomyopathy is most commonly confirmed by 2D echocardiography and usually recognized as a left ventricular wall thickness >15 mm. This imaging technique can not only unearth the presence and severity of hypertrophy but also that of left ventricular outflow obstruction. Approximately, one quarter of all patients with hypertrophic cardiomyopathy will have a resting gradient (>30 millimeters mercury [mm Hg]). It is important to note that a left ventricular wall thickness >30 mm and an outflow obstruction gradient >30 mm Hg are both independently associated with a greater risk for sudden cardiac death.
In some cases, there is diffuse hypertrophy, but it is common to have only one area that exhibits evidence of wall thickening. A large proportion will have no gradient or only a gradient that manifests during maneuvers that simulate exertion. In these cases, evidence of left ventricular hypertrophy supports the diagnosis. When there is suspicion for hypertrophic cardiomyopathy but no evidence on echocardiography, magnetic resonance imaging of the heart can be useful in identifying the asymmetric areas of hypertrophy common in this disease.
A. History Part I: Pattern Recognition:
Unfortunately, as researchers have gathered more information about hypertrophic cardiomyopathy, it has become increasingly clear that there is no “typical” presentation. Over the course of their lives, patients can have varying presentations ranging from no pathology, to atrial fibrillation to congestive heart failure, to sudden cardiac death.
In general, the older a patient is with this diagnosis the more likely it is that the patient will not manifest the more malignant side effects of this disease process. Perhaps the most important identifying feature of this disease is recognizing when a patient has a family history of hypertrophic cardiomyopathy. This allows for testing of other relatives and periodic screening to identify disease progression.
B. History Part 2: Prevalence:
Hypertrophic cardiomyopathy is an autosomal dominant disease that has a prevalence of 1 in 500 adults.
C. History Part 3: Competing diagnoses that can mimic hypertrophic cardiomyopathy.
When outflow obstruction is present, this disease process can sometimes be confused with aortic stenosis on physical exam. Furthermore, a focused history should be taken to determine if patients have an underlying cause for their ventricular hypertrophy, for example a history of systemic hypertension or reasons for infiltrative heart disease.
D. Physical Examination Findings.
The most recognizable physical exam findings of hypertrophic cardiomyopathy are those correlated with outflow obstruction. When outflow obstruction is present, it is possible to hear a systolic crescendo-decrescendo murmur similar to that of aortic stenosis. but it is heard best at the left lower sternal border on auscultation. This murmur can be distinguished from aortic stenosis, however, in that it becomes less intense with maneuvers that increase venous return or vascular resistance as with squatting or hand grip, and becomes more prominent and harsh with maneuvers that decrease ventricular filling as with the Valsalva maneuver or standing up from a squatting position. In these instances, the practitioner should listen for a murmur of aortic insufficiency since this can be present as well. When severe outflow obstruction is present, S2 may be paradoxically split due to the prolonged outflow time from the obstruction to flow.
Other physical exam findings that are consistent with hypertrophic cardiomyopathy include a prominent jugular a wave due to hypertrophy and poor right ventricle compliance. Due to hypertrophy, a heave may be present and the point of maximal impulse is often diffuse and displaced. Carotid pulsation has a classic bifid pattern which is a rapid upstroke followed by a second peak.
It should be noted that there are patients with genotype positive hypertrophic cardiomyopathy that have no or minimal physiologic expression of their disease. These patients may have no abnormal physical exam findings although they do have the diagnosis of hypertrophic cardiomyopathy.
E. What diagnostic tests should be performed?
Since there are patients with this disease process that have no physical manifestations of the disease, there is not a physical exam finding that confirms the diagnosis. Instead, exam findings of ventricular hypertrophy in the proper setting should lead a clinician to get imaging studies to aid in diagnosis. Please see the section on imaging studies for further information about tests that are useful to order.
1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Genetic testing may be useful to help identify patients that have mutations that portend a higher likelihood of sudden cardiac death. For example, beta myosin heavy chain mutations and troponin T mutations may be associated with higher rates of sudden death. However, elderly patients identified with this disease often have minimal symptoms, even when outflow gradients are present. These patients commonly have mutations in cardiac myosin binding protein C and troponin I genes. Once a patient with hypertrophic cardiomyopathy has been identified it is important to test their first degree relatives for this disease.
2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Two dimensional echocardiography is the diagnostic modality of choice for this disease. It is widely available and efficient at diagnosing ventricular hypertrophy. Hypertrophic cardiomyopathy can present with just a genotype diagnosis and no initial evidence of hypertrophy on echocardiogram.
In fact, hypertrophy is often first apparent during late adolescence. Patients also have varying degrees of hypertrophy ranging from mild (13-15mm) to massive (>30mm). Hypertrophy can be diffuse or only be found in specific segments of the myocardium. If hypertrophy is present in only one area, it is found in decreasing order in the septum, apex, and the mid-ventricle respectively. When echocardiography does not identify hypertrophy, magnetic resonance imaging (MRI) can be useful in identifying specific segments of hypertrophy that may be missed with the aforementioned modality.
Transthoracic echocardiography can also be used to diagnose left ventricular outflow tract obstruction which is defined as an outflow tract gradient >30 mm Hg at rest or with provocation.
While electrocardiograms are often abnormal in patients with hypertrophic cardiomyopathy, there is no clear pattern that will aid in the diagnosis of this disease. In fact, there is no association between voltage on electrocardiogram and degree of hypertrophy on echocardiograph.
F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
III. Default Management.
Management of hypertrophic cardiomyopathy is determined by symptom manifestation. In patients that are asymptomatic without concerning risk factors for sudden cardiac death there is no evidence that prophylactic therapy makes any difference in disease progression.
In asymptomatic patients with very large (> 35mm) left ventricular hypertrophy, initiation of medical therapy may help delay the onset of symptoms. However, there is minimal data to support this assertion. The vast majority of patients do not have massive hypertrophy and management is targeted at control of symptoms of heart failure, ischemia, atrial fibrillation and prevention of sudden cardiac death. Largely these are managed through medical therapy; however, in certain instances surgical intervention may be useful.
A. Immediate management.
Patients that present to the hospital with hypertrophic cardiomyopathy will likely be presenting due to a heart failure exacerbation. Since the majority of patients have diastolic heart failure, management is based on relieving outflow track obstruction (when present), controlling hypertension and relieving congestion. Symptom management has been best described by use of beta-blockade as well as non-dihydropyridines (specifically Verapamil).
These medications slow heart rate leading to a prolongation in diastole and increased ventricular filling time. This in turn leads to greater cardiac output. In patients that are experiencing chest pain these medicines also decrease the cardiac muscle’s demand for oxygen, leading to reduced ischemia. Diuresis with loop diuretics is advisable in patients that have evidence of volume overload, but they should be used cautiously as to not decrease preload too dramatically.
These patients are also very sensitive to loss of their atrial kick, and may present with an exacerbation during an episode of atrial fibrillation. Patients with hypertrophic cardiomyopathy are prone to episodes of atrial fibrillation. Due to wall hypertrophy and their dependence on ventricular filling to get adequate cardiac output, a rapid ventricular rate can make patients quite symptomatic.
As in the general population, medical therapy to control the ventricular rate with beta-blockade or a non-dihydropyridine is the first line of therapy. If patients fail medical management and remain symptomatic atrioventricular (AV) node ablation and pacemaker implantation may be necessary to prevent episodes of tachycardia. Unlike the general population, patient’s with hypertrophic cardiomyopathy are more likely to develop thrombus with systemic embolization. Therefore, practitioners should have a very low threshold for initiating anticoagulation therapy.
B. Physical Examination Tips to Guide Management.
Practitioners should pay close attention to signs of volume overload. They should monitor lung sounds for evidence of crackles indicating pulmonary edema. Furthermore, a thorough cardiac exam daily will help with management. Assessing degree of jugular venous distention and edema will help determine the extent of congestion that a patient is experiencing. Furthermore, cardiac auscultation should be used to ensure a patient is in sinus rhythm, or rate controlled if they are experiencing atrial fibrillation.
C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.
As with congestive heart failure exacerbations in patients without hypertrophic cardiomyopathy, response to treatment can be monitored by symptom resolution and improvement in physical exam findings of venous congestion. There is no laboratory test or diagnostic study that needs to be followed on a regular basis to determine resolution of an exacerbation. However, in patients being treated with diuresis it may be wise to follow electrolyte levels and monitor kidney function to ensure patients are not pushed into a pre-renal state due to diuresis.
D. Long-term management.
Medical management of heart failure symptoms should be initiated as outlined in the immediate management section. There is no evidence that beta-blockers or non dihydropyridines are more efficacious at treating symptoms. It is often based on physician preference and monitoring symptom control in patients. If these medications do not relieve symptoms of heart failure or chest pain then disopyramide, an antiarrhythmic agent, may be considered.
In patients with an outflow gradient, this medication may reduce and help relieve symptoms. Usually patients have evidence of diastolic heart failure, but there are those that progress to systolic dysfunction as well. In this small but important patient population the usual management of systolic heart failure should be initiated. This includes the addition of angiotensin converter enzyme inhibitors, beta-blockade, and in certain instances aldosterone inhibitors and long acting nitrates in combination with hydralazine.
In patients that have an outflow tract obstruction and remain symptomatic despite medical therapy, surgical intervention can be considered. In patients with a gradient of over 50 mm Hg and severe heart failure symptoms, surgery can help reduce these symptoms. Myotomy-myectomy is a surgical procedure where a small amount of septal tissue is removed in order to reduce or abolish the outflow obstruction. When performed by an experienced surgeon, it has a less than 2% mortality rate and can reduce or abolish symptoms in up to 90% of cases. In some cases, replacement of the mitral valve can be performed to help reduce the outflow tract obstruction.
There are also percutaneous procedures that have been used to reduce outflow tract obstructions in patients that remain symptomatic on medical therapy. Septal alcohol ablation is a technique used by cardiologist to reduce outflow gradients for symptom relief. In experienced centers the results can be as effective as myotomy-myectomy surgeries and can be considered for patients that have high surgical risk factors. Patients without outflow tract obstruction that remain symptomatic despite optimal medical management may need to be considered for heart transplantation.
The other subset of patients that require intervention are those patients that are at risk for ventricular arrhythmias, and possible sudden cardiac death. Sudden cardiac death is the most feared outcome of hypertrophic cardiomyopathy. It often occurs in younger patients during times of rest or minimal exertion.
Amongst the general population of patients with hypertrophic cardiomyopathy the annual mortality rate is about 1%. However, there is a subset of patients, compromising about 10% to 20%, that are at much higher risk for sudden cardiac death with an annual rate of up to 5%. Genetic testing is beginning to reveal the mutations that are most commonly associated with sudden cardiac death which include: beta myosin heavy chain and troponin T. There are also clinical risk factors that convey a higher risk of sudden cardiac death.
In a patient with a diagnosis of hypertrophic cardiomyopathy, these high-risk factors include a prior cardiac arrest, family history of premature cardiac death, spontaneous sustained ventricular tachycardia or multiple episodes of nonsustained ventricular tachycardia on Holter monitor, multiple episodes of syncope or pre-syncope, extreme left ventricular hypertrophy (wall thickness >30 mm), or exercise induced hypotension. It is in these high-risk patients that physicians should consider placement of implantable defibrillator devices or anti-arrhythmia therapy with amiodarone.
IV. Management with Co-Morbidities
A. Renal Insufficiency.
Ensure to dose medications appropriately.
B. Liver Insufficiency.
No change in standard management.
C. Systolic and Diastolic Heart Failure
This disease leads to diastolic heart failure, and in rare instances progresses to systolic heart failure. Please see the management section for discussion of the treatment of these diseases in the setting of hypertrophic cardiomyopathy.
D. Coronary Artery Disease or Peripheral Vascular Disease
Patients that are proceeding to surgery to treat symptomatic and refractory outflow tract obstruction should be evaluated for coronary artery disease prior to surgical intervention. If necessary bypass surgery may need to be performed concurrently with myotomy-myomectomy.
E. Diabetes or other Endocrine issues
No change in standard management.
Patients that have manifestations of systolic heart failure due to hypertrophic cardiomyopathy may have limitations in the chemotherapeutic agents they can be administered.
G. Immunosuppression (HIV, chronic steroids, etc).
No change in standard management.
H. Primary Lung Disease (COPD, Asthma, ILD)
Take into consideration the presence of lung disease if treatment for possible ventricular arrhythmias is being pursued, this may argue against using amiodarone.
I. Gastrointestinal or Nutrition Issues
No change in management.
J. Hematologic or Coagulation Issues
No change in management.
K. Dementia or Psychiatric Illness/Treatment
No change in management.
V. Transitions of Care
A. Sign-out considerations While Hospitalized.
Patients with hypertrophic cardiomyopathy frequently experience atrial fibrillation. They are also more prone to clot formation leading to risk of thromboembolic events. If a patient goes into atrial fibrillation while the patient is being cross covered, it may be prudent to have the patient started on therapeutic anticoagulation despite their CHADS2 (congestive heart failure, hypertension, age (75 years old, diabetes mellitus, stroke/transient ischemic attack) score.
B. Anticipated Length of Stay.
Length of stay will be largely determined by the manifestations of hypertrophic cardiomyopathy with which the patient presents. If patients are in decompensated heart failure then their length of stay should mimic those of other patients admitted for decompensated heart failure.
C. When is the Patient Ready for Discharge.
The patient is ready for discharge when they display a normal volume status with their baseline functional capacity. Furthermore, they should be rate controlled and likely anticoagulated if they present with atrial fibrillation.
D. Arranging for Clinic Follow-up
Patients should follow with a primary care provider, and be seen by a cardiologist.
1. When should clinic follow-up be arranged and with whom.
Patients should follow with cardiology and general medicine. There is no defined time for a patient to follow with these specialists after discharge. It will vary widely based on the symptoms they demonstrate related to their hypertrophic cardiomyopathy and their reason for admission.
2. What tests should be conducted prior to discharge to enable best clinic first visit.
3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.
E. Placement Considerations.
Patients with hypertrophic cardiomyopathy will most likely live independently at home following hospitalization.
F. Prognosis and Patient Counseling.
Prognosis varies widely based on the patients’ particular manifestations of hypertrophic cardiomyopathy. In general, the majority of patients with this disease have a very good prognosis with normal life expectancy and minimal symptoms.
VI. Patient Safety and Quality Measures
A. Core Indicator Standards and Documentation.
Follow systolic heart failure core measures if the patient has progressed to systolic heart failure.
B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.
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- I. What every physician needs to know.
- II. Diagnostic Confirmation: Are you sure your patient has hypertrophic cardiomyopathy?
- A. History Part I: Pattern Recognition:
- B. History Part 2: Prevalence:
- C. History Part 3: Competing diagnoses that can mimic hypertrophic cardiomyopathy.
- D. Physical Examination Findings.
- E. What diagnostic tests should be performed?
- 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
- III. Default Management.
- A. Immediate management.
- B. Physical Examination Tips to Guide Management.
- C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.
- D. Long-term management.
- IV. Management with Co-Morbidities
- A. Renal Insufficiency.
- B. Liver Insufficiency.
- C. Systolic and Diastolic Heart Failure
- D. Coronary Artery Disease or Peripheral Vascular Disease
- E. Diabetes or other Endocrine issues
- F. Malignancy
- G. Immunosuppression (HIV, chronic steroids, etc).
- H. Primary Lung Disease (COPD, Asthma, ILD)
- I. Gastrointestinal or Nutrition Issues
- J. Hematologic or Coagulation Issues
- K. Dementia or Psychiatric Illness/Treatment
- V. Transitions of Care
- A. Sign-out considerations While Hospitalized.
- B. Anticipated Length of Stay.
- C. When is the Patient Ready for Discharge.
- D. Arranging for Clinic Follow-up
- 1. When should clinic follow-up be arranged and with whom.
- 2. What tests should be conducted prior to discharge to enable best clinic first visit.
- 3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.
- E. Placement Considerations.
- F. Prognosis and Patient Counseling.
- VI. Patient Safety and Quality Measures
- A. Core Indicator Standards and Documentation.
- B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.