Left ventricular hypertrophy (LVH) is a common finding when there is an increase in left ventricular mass, either due to an increase in wall thickness or due to left ventricular cavity enlargement, or both, in response to a wide array of pathophysiological stressors. |
In this review, we summarize different etiologies of LVH and its complications, and outline the treatment and management options according to etiologies. We also describe the effect of therapy to reduce LVH and the impact on outcome. |
Pertinent studies and ongoing trials of certain drug treatments have been summarized according to LVH pathologies. |
Management of LVH involves lifestyle changes and medications, and may also include surgery and an implantable device for the prevention of sudden cardiac death depending upon the underlying cause. |
Introduction
Causes of LVH
LVH due to pressure/volume overload | Other risk factors for LVH | Infiltrative cardiac processes |
---|---|---|
Systemic hypertension | Athletic training | Amyloidosis |
Aortic stenosis (valvular, supravalvular, subvalvular) | Obesity | Sarcoidosis |
Aortic and mitral regurgitation | Obstructive sleep apnea | Hemochromatosis |
Cardiomyopathies | Chronic kidney disease | Fabry disease |
Ventricular septal defect | Diabetes mellitus | |
Tobacco use | ||
Sodium intake |
Prognosis and pathophysiology of LVH
Treatments
Treatment of LVH in Hypertension
Treatment of Risk Factors for LVH
Treatment of LVH in Aortic Stenosis
Hypertrophic Cardiomyopathy
Changes in cardiac function | Symptoms |
---|---|
Impaired relaxation | Reduced exercise capacity |
Reduced compliance of LV | Exertional dyspnea |
LVOT obstruction | Presyncope/syncope |
Mitral regurgitation | Palpitation, arrhythmias |
Microvascular dysfunction | Chest pain |
Subendocardial ischemia | Heart failure symptoms |
Pharmacotherapy
Medical therapy | Recommendations |
---|---|
Beta adrenergic receptor blockers (without intrinsic sympathetic activity) | • Cornerstone of pharmacological treatment • Relief of ischemic chest discomfort • Recommended in patients in nonobstructive HCM with preserved EF and symptoms of exertional angina or dyspnea * May attenuate exercise-induced LVOT obstruction and dyspnea |
Disopyramide | • A negative inotropic agent • By adding to a beta blocker symptomatic relief can be provided in LVOT obstruction |
L-type calcium channel blockers (verapamil, diltiazem) | • May be beneficial in patients who do not tolerate or respond to beta blockers • Harmful for patients with HOCM and severe dyspnea at rest, also in patients with very high resting gradients or hypotension |
Diuretics | • Effective in low doses • Avoid hypovolemia, hypotension, and intensification or provocation of LVOT obstruction |
Phenylephrine (intravenous) (or other vasoconstrictors without inotropic activity) | • Is recommended alone or in combination with beta blockers • Can be used in obstructive HCM and in patients with acute hypotension who do not respond to fluid administration |
Vasodilators (e.g, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers) or digoxin | • Can worsen symptoms caused by dynamic outflow tract obstruction |
Management of atrial fibrillation in HCM
Heart Failure Therapies and Device Therapy
High-risk clinical features | Primary prevention |
---|---|
Unexplained syncope (≥ 1 recent episodes of syncope suspected by clinical history to be arrhythmic in the previous 6 months) | An ICD is reasonable (2a) |
Apical aneurysm | |
Left ventricular EF < 50% | |
Massive (≥ 30 mm) thickness of the interventricular septum | |
A family history of HCM (≥ 1 first-degree relative or close relatives who are ≤ 50 years of age) with SCD | |
Multiple episodes of documented NSVT (detected with continuous ambulatory ECG monitoring) | An ICD may be considered (2b) |
Late gadolinium enhancement determined by CMRI (≥ 15% of the LVM) |
Septal Reduction Therapy and Surgical Myectomy
Treatment of Ventricular Arrhythmia
Comorbid Conditions
Pregnancy
Future Treatments
Inhibition of actin-myosin cross-bridging | Mechanism of action | Studies |
---|---|---|
Mavacamten (MyoKardia, Inc., South San Francisco, CA, USA) | • Allosteric modulator of cardiac β-myosin • Causes reversible inhibition of actin–myosin cross bridging | • Phase IIa trial of mavacamten -oHMC (PIONEER-HCM; ClinicalTrials.gov Identifier: NCT02842242) [78] • Phase III trial-oHCM (EXPLORER-HCM) [79] |
CK-274 (Cytokinetics, Inc., South San Francisco, CA, USA) | • Is currently under development | • Ongoing phase II clinical trial in obstructive HCM |
Myocardial energetics | ||
Perhexiline | • Used as an antianginal therapy • Oral inhibitor of carnitine palmitoyl transferase I (CPT-1) • Studied for use in noHCM | • METAL-HCM study [82] |
Trimetazidine | • Studied for use in noHCM | |
Ion channels | ||
Ranolazine | • Inhibitors of INaL • Studied for use in noHCM | • RESTYLE-HCM [83] |
Eleclazine | • Inhibitors of INaL • Studied in noHCM and oHCM | • LIBERTY-HCM [84] |
Radiofrequency Ablation
Other Novel Therapies
Fabry Disease and Left Ventricular Hypertrophy
Management
Enzyme Replacement Therapy
-
agalsidase alfa (ReplagalTM, Shire): 0.2 mg/kg as an intravenous infusion given over 40 min every 2 weeks;
-
agalsidase beta (FabrazymeTM, Genzyme): 1 mg/kg as an intravenous infusion over a mean of 2-2.5 h every 2 weeks.
Chaperone Therapy
Cardiac Amyloidosis
Immunoglobulin-Derived Amyloid Light-Chain Amyloidosis
Treatment
Transthyretin Amyloidosis and Treatment
Transthyretin Amyloidosis
Disease-modifying therapies | Mechanism of action | Indication | Available or future therapies |
---|---|---|---|
Synthesis suppression | Reduce the production of mutated and overall TTR | ||
Genetic silencers | |||
Patisiran | • BOTH Cardiomyopathy and Polyneuropathy stage 1 • ONLY Polyneuropathy stage 1 and stage 2 | • Effective in ATTRv Neuro clinical trials • Ongoing ATTR trials | |
Inotersen | • ONLY Polyneuropathy stage 1 and stage 2 | • Effective in ATTRv Neuro clinical trials | |
Vutrisiran | • Ongoing ATTR trials | ||
TTR-LRx | • Ongoing ATTR trials | ||
- Liver transplantation | • Available without clinical trials | ||
- Genetic editing | |||
TTR stabilization | Stabilize circulating TTR, prevent their dissociation or cleavage into amyloidogenic fragments | ||
Tafamidis | • ONLY Cardiomyopathy in ATTRv and ATTR wt • BOTH Cardiomyopathy and Polyneuropathy stage 1 • ONLY Polyneuropathy stage 1 | • Effective in ATTRv Neuro clinical trials • Effective in ATTR CARDIAC clinical trials | |
Diflusinal | • Available without clinical trials • Effective in ATTRv Neuro clinical trials | ||
Acoramidis | • Ongoing ATTR trials | ||
Elimination of deposits | Directed to remove amyloid fibrils | ||
Doxycicline | • Available without clinical trials | ||
Doxycicline-TUDCA | |||
ECGC (green tea) | • Available without clinical trials | ||
Antibodies | |||
- PRXOO4 | |||
- NI006 |