Guidelines on the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ­ 2024 / Diretriz sobre Diagnóstico e Tratamento da Cardiomiopatia Hipertrófica ­ 2024

Hypertrophic cardiomyopathy (HCM) is a form of genetically caused heart muscle disease, characterized by the thickening of the ventricular walls. Diagnosis requires detection through imaging methods (Echocardiogram or Cardiac Magnetic Resonance) showing any segment of the left ventricular wall with a thickness > 15 mm, without any other probable cause. Genetic analysis allows the identification of mutations in genes encoding different structures of the sarcomere responsible for the development of HCM in about 60% of cases, enabling screening of family members and genetic counseling, as an important part of patient and family management. Several concepts about HCM have recently been reviewed, including its prevalence of 1 in 250 individuals, hence not a rare but rather underdiagnosed disease. The vast majority of patients are asymptomatic. In symptomatic cases, obstruction of the left ventricular outflow tract (LVOT) is the primary disorder responsible for symptoms, and its presence should be investigated in all cases. In those where resting echocardiogram or Valsalva maneuver does not detect significant intraventricular gradient (> 30 mmHg), they should undergo stress echocardiography to detect LVOT obstruction. Patients with limiting symptoms and severe LVOT obstruction, refractory to beta-blockers and verapamil, should receive septal reduction therapies or use new drugs inhibiting cardiac myosin. Finally, appropriately identified patients at increased risk of sudden death may receive prophylactic measure with implantable cardioverter-defibrillator (ICD) implantation.

La miocardiopatía hipertrófica (MCH) es una forma de enfermedad cardíaca de origen genético, caracterizada por el engrosamiento de las paredes ventriculares. El diagnóstico requiere la detección mediante métodos de imagen (Ecocardiograma o Resonancia Magnética Cardíaca) que muestren algún segmento de la pared ventricular izquierda con un grosor > 15 mm, sin otra causa probable. El análisis genético permite identificar mutaciones en genes que codifican diferentes estructuras del sarcómero responsables del desarrollo de la MCH en aproximadamente el 60% de los casos, lo que permite el tamizaje de familiares y el asesoramiento genético, como parte importante del manejo de pacientes y familiares. Varios conceptos sobre la MCH han sido revisados recientemente, incluida su prevalencia de 1 entre 250 individuos, por lo tanto, no es una enfermedad rara, sino subdiagnosticada. La gran mayoría de los pacientes son asintomáticos. En los casos sintomáticos, la obstrucción del tracto de salida ventricular izquierdo (TSVI) es el trastorno principal responsable de los síntomas, y su presencia debe investigarse en todos los casos. En aquellos en los que el ecocardiograma en reposo o la maniobra de Valsalva no detecta un gradiente intraventricular significativo (> 30 mmHg), deben someterse a ecocardiografía de esfuerzo para detectar la obstrucción del TSVI. Los pacientes con síntomas limitantes y obstrucción grave del TSVI, refractarios al uso de betabloqueantes y verapamilo, deben recibir terapias de reducción septal o usar nuevos medicamentos inhibidores de la miosina cardíaca. Finalmente, los pacientes adecuadamente identificados con un riesgo aumentado de muerte súbita pueden recibir medidas profilácticas con el implante de un cardioversor-desfibrilador implantable (CDI).

A cardiomiopatia hipertrófica (CMH) é uma forma de doença do músculo cardíaco de causa genética, caracterizada pela hipertrofia das paredes ventriculares. O diagnóstico requer detecção por métodos de imagem (Ecocardiograma ou Ressonância Magnética Cardíaca) de qualquer segmento da parede do ventrículo esquerdo com espessura > 15 mm, sem outra causa provável. A análise genética permite identificar mutações de genes codificantes de diferentes estruturas do sarcômero responsáveis pelo desenvolvimento da CMH em cerca de 60% dos casos, permitindo o rastreio de familiares e aconselhamento genético, como parte importante do manejo dos pacientes e familiares. Vários conceitos sobre a CMH foram recentemente revistos, incluindo sua prevalência de 1 em 250 indivíduos, não sendo, portanto, uma doença rara, mas subdiagnosticada. A vasta maioria dos pacientes é assintomática. Naqueles sintomáticos, a obstrução do trato de saída do ventrículo esquerdo (OTSVE) é o principal distúrbio responsável pelos sintomas, devendo-se investigar a sua presença em todos os casos. Naqueles em que o ecocardiograma em repouso ou com Manobra de Valsalva não detecta gradiente intraventricular significativo (> 30 mmHg), devem ser submetidos à ecocardiografia com esforço físico para detecção da OTSVE.   Pacientes com sintomas limitantes e grave OTSVE, refratários ao uso de betabloqueadores e verapamil, devem receber terapias de redução septal ou uso de novas drogas inibidoras da miosina cardíaca. Por fim, os pacientes adequadamente identificados com risco aumentado de morta súbita podem receber medida profilática com implante de cardiodesfibrilador implantável (CDI).

Association of duration and intensity of exercise with phenotypic expression in hypertrophic cardiomyopathy.

OBJECTIVES: There is limited data regarding the impact of exercise on phenotypic expression in hypertrophic cardiomyopathy (HCM). We aimed to investigate whether such an association exists in a cohort of genotype-positive HCM patients. METHODS: In this cross-sectional study of genotype-positive HCM families, we used structured questionnaires to obtain data regarding intensity and duration of exercise of participants starting at the age of 10, as well as data regarding exercise recommendations and their impact on quality of life (QOL). The association of cumulative metabolic-equivalent hours of exercise at different ages with different measures of phenotypic expression (maximal wall thickness, left atrial diameter, extent of late gadolinium enhancement) was analyzed. RESULTS: The study included 109 patients from 55 families, including 43 male (39%) and 90 (83%) phenotype-positive. No association was identified between exercise duration or intensity with any of the phenotypic markers with the exception of greater cumulative exercise associated with younger age at presentation. Similar results were obtained when analysis was limited to exercise until the age of 20, until the age of 30 or only after 30. Among phenotype-positive patients, 89% recalled receiving recommendations regarding exercise restriction, 29% noted reduction in exercise level following such recommendations and 25% noted this having a significant impact on their QOL. CONCLUSION: We found no association between exercise intensity or duration and phenotypic expression in genotype-positive HCM patients. These findings are important for physician-patient discussions and support the recent trend towards more permissive exercise restrictions in HCM.

Clinical Significance of Postoperative Atrial Fibrillation in Hypertrophic Cardiomyopathy Patients Undergoing Septal Myectomy.

BACKGROUND: The optimal management of hypertrophic cardiomyopathy (HCM) patients with postoperative atrial fibrillation (POAF) after surgical myectomy remains unknown. We sought to investigate the association between POAF and atrial fibrillation (AF) or cardioembolic events during follow-up to bridge this gap. METHODS: Patients undergoing surgical myectomy at 2 HCM referral centres in North America from 2002 to 2020 were included in this study. Patients with preoperative AF were excluded. POAF was defined as any episode of AF within 30 days after surgery. RESULTS: Of 1176 patients, 375 (31.9%) had POAF. Age (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P < 0.001), premyectomy left atrial diameter (LAD; adjusted HR 1.6, 95% CI 1.32-2.02; P < 0.001), and smoking (adjusted HR 1.60, 95% CI 1.17-2.20; P = 0.001) were associated with POAF on multivariable analysis. Of 934 patients with follow-up data, of duration 4.3 ± 4.1 years, AF was detected in 86 (9.2%). Only POAF (HR 4.20, 95% CI 2.44-7.23; P < 0.001), previous history of stroke (HR 4.81, 95% CI 1.63-14.17; P = 0.01), and postmyectomy LAD (HR 1.80, 95% CI 1.21-2.70; P = 0.004) were associated with AF incidence during follow-up. Cardioembolic events occurred in only 15 patients (1.6%). POAF was not associated with increased cardioembolic risk, with only 3 patients with POAF suffering such an event, all more than 4 years after surgery. CONCLUSIONS: POAF is common in HCM patients undergoing myectomy and is a predictor of AF during follow-up. Over long-term follow-up, cardioembolic events are uncommon. These findings suggest that routine long-term anticoagulation for all HCM patients with postmyectomy AF is not justified after the initial postoperative period.

Patient Outcomes and Characteristics in a Contemporary Quaternary Canadian Cardiac Intensive Care Unit.

Background: The modern-day cardiac intensive care unit (CICU) has evolved to care for patients with acute critical cardiac illness. We describe the current population of cardiac patients in a quaternary CICU. Methods: Consecutive CICU patients admitted to the CICU at the Toronto General Hospital from 2014 to 2020 were studied. Patient demographics, admission diagnosis, critical care resources, complications, in-hospital mortality, and CICU and hospital length of stay were recorded. Results: A total of 8865 consecutive admissions occurred, with a median age of 64.9 years. The most common primary cardiac diagnoses were acute decompensated heart failure (17.8%), non ST-elevation myocardial infarction (16.8%), ST-elevation myocardial infarction (15.5%), and arrhythmias (14.7%). Cardiogenic shock was seen in 13.2%, and out-of-hospital cardiac arrest in 4.1%. A noncardiovascular admission diagnosis accounted for 13.9% of the cases. Over the period studied, rates of admission were higher for cardiogenic shock (P < 0.001 for trend), with a higher use of critical care resources. Additionally, rates of admission were higher in female patients and those who had chronic kidney disease and diabetes. The in-hospital mortality rate of all CICU admissions was 13.2%, and it was highest in those with noncardiac conditions, compared to the rate in those with cardiac diagnoses (29.4% vs 10.6%, P < 0.001). Conclusions: Given the trends of higher acuity of patients with cardiac critical illness, with higher use of critical care resources, education streams for critical care within cardiology, and alternative pathways of care for patients who have lower-acuity cardiac disease remain imperative to manage this evolving population.

Introduction: L'unité de soins intensifs de cardiologie (USIC) d'aujourd'hui a évolué vers des soins aux patients atteints d'une maladie cardiaque aiguë en phase critique. Nous décrivons la population actuelle de patients cardiaques d'une USIC quaternaires. Méthodes: Les patients consécutifs d'USIC admis à l'USIC de l'Hôpital général de Toronto de 2014 à 2020 ont fait l'objet de l'étude. Les données démographiques des patients, le diagnostic à l'admission, les ressources en soins aux patients en phase critique, les complications, la mortalité intrahospitalière, et la durée de séjour à l'hôpital et à l'USIC ont été enregistrés. Résultats: Il y a eu un total de 8 865 admissions consécutives dont les patients avaient un âge médian de 64,9 ans. Les diagnostics principaux les plus fréquents de maladies cardiaques étaient l'insuffisance cardiaque aiguë décompensée (17,8 %), l'infarctus du myocarde sans élévation du segment ST (16,8 %), l'infarctus du myocarde avec élévation du segment ST (15,5 %) et les arythmies (14,7 %). Le choc cardiogénique a été observé chez 13,2 %, et l'arrêt cardiaque hors de l'hôpital, chez 4,1 %. Un diagnostic d'admission de maladie non cardiovasculaire représente 13,9 % des cas. Durant la période étudiée, les taux d'admission en raison d'un choc cardiogénique étaient plus élevés (P < 0,001 pour la tendance), et entraînaient une utilisation plus élevée de ressources en soins aux patients en phase critique. De plus, les taux d'admission étaient plus élevés chez les patientes, et chez ceux qui avaient une insuffisance rénale chronique et un diabète. Le taux de mortalité intrahospitalière de toutes les admissions à l'USIC était de 13,2 %, et il constituait le taux le plus élevé chez ceux qui avaient des maladies non cardiaques comparativement au taux chez ceux qui avaient des diagnostics de maladies cardiaques (29,4 % vs 10,6 %, P < 0,001). Conclusions: Compte tenu des tendances d'accroissement de la gravité de l'état des patients atteints d'une maladie cardiaque en phase critique et de la plus grande utilisation des ressources en soins aux patients en phase critique, des volets de formation en soins aux patients en phase critique en cardiologie et d'autres protocoles de soins des patients qui ont une maladie cardiaque de plus faible gravité demeurent essentiels à la prise en charge de cette population grandissante.

Clonal hematopoiesis confers an increased mortality risk in orthotopic heart transplant recipients.

Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p < .001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p = .008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4-6.3; p = .003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality.

Clonal haematopoiesis is associated with higher mortality in patients with cardiogenic shock.

AIMS: Cardiogenic shock (CS) with variable systemic inflammation may be responsible for patient heterogeneity and the exceedingly high mortality rate. Cardiovascular events have been associated with clonal haematopoiesis (CH) where specific gene mutations in haematopoietic stem cells lead to clonal expansion and the development of inflammation. This study aims to assess the prevalence of CH and its association with survival in a population of CS patients in a quaternary centre. METHODS AND RESULTS: We compared the frequency of CH mutations among 341 CS patients and 345 ambulatory heart failure (HF) patients matched for age, sex, ejection fraction, and HF aetiology. The association of CH with survival and levels of circulating inflammatory cytokines was analysed. We detected 266 CH mutations in 149 of 686 (22%) patients. CS patients had a higher prevalence of CH-related mutations than HF patients (odds ratio 1.5; 95% confidence interval [CI] 1.0-2.1, p = 0.02) and was associated with decreased survival (30 days: hazard ratio [HR] 2.7; 95% CI 1.3-5.7, p = 0.006; 90 days: HR 2.2; 95% CI 1.3-3.9, p = 0.003; and 3 years: HR 1.7; 95% CI 1.1-2.8, p = 0.01). TET2 or ASXL1 mutations were associated with lower survival in CS patients at all time-points (p ≤ 0.03). CS patients with TET2 mutations had higher circulating levels of SCD40L, interferon-γ, interleukin-4, and tumour necrosis factor-α (p ≤ 0.04), while those with ASXL1 mutations had decreased levels of CCL7 (p = 0.03). CONCLUSIONS: Cardiogenic shock patients have high frequency of CH, notably mutations in TET2 and ASXL1. This was associated with reduced survival and dysregulation of circulating inflammatory cytokines in those CS patients with CH.

Admission Bedside Lung Ultrasound Reclassifies Mortality Prediction in Patients With ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Early risk stratification is essential for in-hospital management of ST-segment-elevation myocardial infarction. Acute heart failure confers a worse prognosis, and although lung ultrasound (LUS) is recommended as a first-line test to assess pulmonary congestion, it has never been tested in this setting. Our aim was to evaluate the prognostic ability of admission LUS in patients with ST-segment-elevation myocardial infarction. METHODS: LUS protocol consisted of 8 scanning zones and was performed before primary percutaneous coronary intervention by an operator blinded to Killip classification. A LUS combined with Killip (LUCK) classification was developed. Receiver operating characteristic and net reclassification improvement analyses were performed to compare LUCK and Killip classifications. RESULTS: We prospectively investigated 215 patients admitted with ST-segment-elevation myocardial infarction between April 2018 and June 2019. Absence of pulmonary congestion detected by LUS implied a negative predictive value for in-hospital mortality of 98.1% (93.1-99.5%). The area under the receiver operating characteristic curve of the LUCK classification for in-hospital mortality was 0.89 (P=0.001), and of the Killip classification was 0.86 (P<0.001; P=0.05 for the difference between curves). LUCK classification improved Killip ability to predict in-hospital mortality with a net reclassification improvement of 0.18. CONCLUSIONS: In a cohort of patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, admission LUS added to Killip classification was more sensitive than physical examination to identify patients at risk for in-hospital mortality. LUCK classification had a greater area under the receiver operating characteristic curve and reclassified Killip classification in 18% of cases. Moreover, absence of pulmonary congestion on LUS provided an excellent negative predictive value for in-hospital mortality.

A Comprehensive and Contemporary Review on Immunosuppression Therapy for Heart Transplantation.

Heart transplantation is the standard of therapy for patients with end-stage heart disease. Since the first human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft function and surveillance of long-term complications have drastically increased recipient survival. However, there are yet many challenges in the modern era of heart transplantation in which immunosuppression may play a key role in further advances in the field. A fine-tuning of immune modulation to prevent graft rejection while avoiding side effects from over immunosuppression has been the vital goal of basic and clinical research. Individualization of drug choices and strategies, taking into account the recipient's clinical characteristics, underlying heart failure diagnosis, immunologic risk and comorbidities seem to be the ideal approaches to improve post-transplant morbidity and survival while preventing both rejection and complications of immunosuppression. The aim of the present review is to provide a practical, comprehensive overview of contemporary immunosuppression in heart transplantation. Clinical evidence for immunosuppressive drugs is reviewed and practical approaches are provided. Cardiac allograft rejection classification and up-to-date management are summarized. Expanding therapies, such as photophoresis, are outlined. Drug-to-drug interactions of immunosuppressive agents focused on cardiovascular medications are summarized. Special situations involving heart transplantation such as sarcoidosis, Chagas diseases and pediatric immunosuppression are also reviewed. The evolution of phamacogenomics to individualize immunosuppressive therapy is described. Finally, future perspectives in the field of immunosuppression in heart transplantation are highlighted.

Expanding benefits from cardiac resynchronization therapy to exercise-induced left bundle branch block in advanced heart failure.

Indications of cardiac resynchronization therapy (CRT) do not include exercise-induced left bundle branch block, but functional impairment could be improved with CRT in such cases. A 57-year-old woman with idiopathic dilated cardiomyopathy (ejection fraction 23%) presented with New York Heart Association Class IV and recurrent hospitalizations. During heart transplant evaluation, a new onset of intermittent left bundle branch block was observed on the cardiopulmonary exercise test. CRT was implanted, and 97% resynchronization rate was achieved. In 12 month follow-up, both clinical and prognostic exercise parameters improved. In patients with heart failure with reduced ejection fraction and no left bundle branch block at rest, exercise test can uncover electromechanical dyssynchrony that may benefit from CRT.