Obstruction in Hypertrophic Cardiomyopathy: Many Faces.

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, exhibits left ventricular hypertrophy not secondary to other causes, with varied phenotypic expression. Enhanced actin-myosin interaction underlies excessive myocardial contraction, frequently resulting in dynamic obstruction within the left ventricle. Left ventricular outflow tract obstruction, occurring at rest or with provocation in 75% of HCM patients, portends adverse prognosis, contributes to symptoms, and is frequently a therapeutic target. Transthoracic echocardiography plays a crucial role in the screening, initial diagnosis, management, and risk stratification of HCM. Herein, we explore echocardiographic evaluation of HCM, emphasizing Doppler assessment for obstruction. Echocardiography informs management strategies through noninvasive hemodynamic assessment, which is frequently obtained with various provocative maneuvers. Recognition of obstructive HCM phenotypes and associated anatomical abnormalities guides therapeutic decision-making. Doppler echocardiography allows monitoring of therapeutic responses, whether it be medical therapies (including cardiac myosin inhibitor therapy) or septal reduction therapies, including surgical myectomy and alcohol septal ablation. This article discusses the hemodynamics of obstruction and practical application of Doppler assessment in HCM. In addition, it provides a visual atlas of obstruction in HCM, including high-quality figures and complementary videos that illustrate the many facets of dynamic obstruction.

Tale of two hearts: a TNNT2 hypertrophic cardiomyopathy case report.

Hypertrophic cardiomyopathy (HCM) is a heritable cardiomyopathy that is predominantly caused by pathogenic mutations in sarcomeric proteins. Here we report two individuals, a mother and her daughter, both heterozygous carriers of the same HCM-causing mutation in cardiac Troponin T (TNNT2). Despite sharing an identical pathogenic variant, the two individuals had very different manifestations of the disease. While one patient presented with sudden cardiac death, recurrent tachyarrhythmia, and findings of massive left ventricular hypertrophy, the other patient manifested with extensive abnormal myocardial delayed enhancement despite normal ventricular wall thickness and has remained relatively asymptomatic. Recognition of the marked incomplete penetrance and variable expressivity possible in a single TNNT2-positive family has potential to guide HCM patient care.

High-Sensitivity Cardiac Troponin T Elevation in Hypertrophic Cardiomyopathy Is Associated With Ventricular Arrhythmias.

OBJECTIVE: To investigate the relationship between high-sensitivity cardiac troponin T (hs-cTnT) levels and sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). METHODS: A referral HCM population with prospectively obtained hs-cTnT concentration from March 1, 2018, to April 23, 2020, was reviewed. Patients with end-stage renal disease or an abnormal hs-cTnT level not collected in an outpatient protocolled fashion were excluded. The hs-cTnT level was compared with demographic characteristics, comorbidities, conventional HCM-associated SCD risk factors, imaging, exercise testing, and prior cardiac events. RESULTS: Of 112 included patients, 69 (62%) had an elevated hs-cTnT concentration. The level of hs-cTnT correlated with known risk factors for SCD, including nonsustained ventricular tachycardia (P=.049) and septal thickness (P=.02). When patients were stratified by having a normal vs an elevated hs-cTnT concentration, patients with elevated hs-cTnT concentration were more likely to have experienced an implantable cardioverter-defibrillator discharge for ventricular arrhythmia, ventricular arrhythmia with hemodynamic instability, or cardiac arrest (incidence rate ratio, 2.96; 95% CI, 1.11 to 10.2). When sex-specific hs-cTnT cutoffs were removed, this association was no longer present (incidence rate ratio, 1.50; 95% CI, 0.66 to 3.60). CONCLUSION: In a protocolized, outpatient HCM population, hs-cTnT elevations were common and were associated with more arrhythmic expressivity of the HCM substrate as indicated by previous ventricular arrhythmias and appropriate implantable cardioverter-defibrillator shocks only when sex-specific hs-cTnT cutoffs were used. Further research should use different hs-cTnT reference values by sex to determine whether an elevated hs-cTnT value is an independent risk factor for SCD in patients with HCM.

Squat-to-stand provocation of dynamic left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: a case report.

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is an important determinant of the management of hypertrophic cardiomyopathy (HCM). With a nationwide shortage of amyl nitrite in 2019, we implemented a 'repetitive squat-to-stand' manoeuvre to provoke LVOT obstruction during echocardiography. CASE SUMMARY: A 64-year-old female was referred with symptomatic HCM refractory to pharmacologic therapy. Transthoracic echocardiography showed minor LVOT obstruction with conventional imaging at rest and during Valsalva manoeuvre, but severe obstruction was confirmed with the repetitive squat-to-stand manoeuvre. Alcohol septal ablation via the first septal perforator was performed with subsequent resolution of symptoms. DISCUSSION: Due to the dynamic nature of LVOT obstruction, a series of provocative manoeuvres including Valsalva manoeuvre, inhalation of amyl nitrite, and exercise are often necessary to maximally augment ventricular obstruction. The recent unavailability of amyl nitrite during a nationwide shortage prompted the implementation of a protocol of repetitive squat-to-stand manoeuvre in our echocardiography laboratory. Rising from the squatting position decreases preload and afterload, both of which augment dynamic LVOT obstruction. Repetition of squatting and standing appears to enhance the sensitivity of the manoeuvre, particularly when exertional symptoms are reproduced. In this case, repetitive squat-to-stand manoeuvre led to the identification of severe LVOT obstruction which may not have been diagnosed otherwise, alteration of treatment to septal reduction therapy, and subsequent resolution of symptoms.

Prolonged QTc interval due to escitalopram overdose.

BACKGROUND: Drugs most commonly responsible for the acquired form of long QT syndrome are antibiotics and antidepressants. Escitalopram overdose leading to prolongation of the QTc interval has only twice been previously described in the literature. METHODS: We report a 33-year-old Caucasian woman who attempted suicide by ingesting 15-20 pills of lithium (300 mg each), 15-20 pills of escitalopram (20 mg each), and alcohol. An electrocardiogram (ECG) on admission to the medicine telemetry unit showed a QTc prolongation of 491 ms and normal sinus rhythm. Repeat ECG 18 hours after admission showed a QTc of 502 ms and sinus bradycardia. Serial ECGs were continued with the following results of QTc/hours after admission: 499 ms/2, 485 ms/25 (> 1 day), 469 ms/41, 461 ms/71, 476 ms/97 (> 4 days). After the QTc interval had declined to 461 ms after more than 2 days (71 hours), the patient was transferred to the inpatient psychiatry ward service. CONCLUSIONS: Prescribers may wish to exercise caution when administering escitalopram to patients who have suicidal ideations and depression. In the event of an overdose, QT prolongation can occur and ECG monitoring should take place for at least 2 days after ingestion in order to prevent life-threatening arrhythmias such as torsades de pointes (tdp). Other factors and drugs that could contribute to prolongation of the QT interval should be taken into account when determining the time period needed for ECG monitoring in the individual patient.

Molecular analysis of inflammatory markers in trauma patients at risk of postinjury complications.

BACKGROUND: Genetic differences associated with individual's immune responses appear to be a major contributing factor to the development of trauma- induced sepsis. Thus, effective treatment of sepsis requires the identification of the patients who are at increased risk for sepsis. METHODS: Sixty-eight patients, of which the majority had an injury severity score >15, and 118 controls from the same geographic region were genotyped. Cytokine and Toll-like receptor (TLR) genotypes and expressions were tested using polymerase chain reaction (PCR). RESULTS: Fifty percent of African American and 42% of Caucasian patients developed posttrauma sepsis. Frequency distribution of the polymorphism for some cytokine genes such as Interleukin (IL)-10 low/high and interferon (IFN)-gamma low producer were statistically different between the septic and aseptic patients, for others, such as tumor necrosis factor (TNF)-alpha, IL-6, and IL-18, there was no statistical difference. The TLR-2 genotypes (A/G) were considered a sepsis risk marker as compared with A/A (62.5% versus 37.5%, p < 0.03; relative risk = 2.5) in African American patients. Cytokine mRNA levels correlated with genotype definition, particularly, for IL-10, IL-6, IL-18, and TNF-alpha. A time course study demonstrated a significant difference in cytokines expression profile in septic and aseptic patients before the development of sepsis. CONCLUSION: Monitoring cytokine expression levels before the disease might predict the outcome of sepsis. A large cohort study is needed to assess the diagnostic potential of the genotypes.