Clonal haematopoiesis is associated with major adverse cardiovascular events in patients with hypertrophic cardiomyopathy.

AIMS: The heterogeneous phenotype of hypertrophic cardiomyopathy (HCM) is still not fully understood. Clonal haematopoiesis (CH) is emerging as a cardiovascular risk factor potentially associated with adverse clinical events. The prevalence, phenotype and outcomes related to CH in HCM patients were evaluated. METHODS AND RESULTS: Patients with HCM and available biospecimens from the Peter Munk Cardiac Centre Cardiovascular Biobank were subjected to targeted sequencing for 35 myeloid genes associated with CH. CH prevalence, clinical characteristics, morphological phenotypes assessed by echocardiogram and cardiac magnetic resonance and outcomes were assessed. All patients were evaluated for a 71-plex cytokines/chemokines, troponin I and B-type natriuretic peptide analysis. Major adverse cardiovascular events (MACE) were defined as appropriate implantable cardioverter-defibrillator shock, stroke, cardiac arrest, orthotopic heart transplant and death. Among the 799 patients, CH was found in 183 (22.9%) HCM patients with sarcomeric germline mutations. HCM patients with CH were more symptomatic and with a higher burden of fibrosis than those without CH. CH was associated with MACE in those HCM patients with sarcomeric germline mutations (adjusted hazard ratio [HR] 6.89, 95% confidence interval [CI] 1.78-26.6; p = 0.005), with the highest risk among those that had DNMT3A, TET2 and ASXL1 mutations (adjusted HR 5.76, 95% CI 1.51-21.94; p = 0.010). Several cytokines (IL-1ra, IL-6, IL-17F, TGFα, CCL21, CCL1, CCL8, and CCL17), and troponin I were upregulated in gene-positive HCM patients with CH. CONCLUSIONS: These results indicate that CH in patients with HCM is associated with worse clinical outcomes. In the absence of CH, gene-positive patients with HCM have lower rates of MACE.

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.

Clinical Characteristics and Prognostic Importance of Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy.

BACKGROUND: Left ventricular (LV) apical aneurysms in hypertrophic cardiomyopathy (HCM) are a recognized risk marker for adverse cardiovascular events. There is variable practice among clinicians and discordance between international guidelines regarding treatment recommendations and prognostication for this important phenotype. OBJECTIVES: The authors sought to describe the morphology, clinical course, and risk of adverse events in a large single-center cohort of HCM patients with LV apical aneurysms. METHODS: This study analyzed 160 HCM patients with an LV apical aneurysm who were evaluated in our dedicated HCM clinic between January 1997 and April 2021. RESULTS: Mean age was 59.1 ± 13.6 years, and 71% of these patients were male. Mean aneurysm size was 1.77 ± 1.04 cm. Over 6.2 ± 4.8 years, 14 (9%) patients had a sudden cardiac death (SCD) event, including appropriate therapy from an implantable cardioverter-defibrillator (ICD) or resuscitation from cardiac arrest (annualized event rate 1.77%/y), 39 (24%) had either a thromboembolic stroke or apical thrombus formation (2.9%/y), and 14 (9%) developed LV systolic dysfunction with an ejection fraction (EF) <50% (1.28%/y). HRs for SCD, stroke or thrombus, and EF <50% per 1-cm increase in aneurysm size were 1.69 (P = 0.007), 1.60 (P = 0.0002), and 1.63 (P = 0.01), respectively. Aneurysm size ≥2 cm was associated with a 5-year SCD rate of 9.7%, compared with 2.9% for aneurysm size <2 cm (log-rank P = 0.037). This subgroup also had higher risk of stroke/thrombus formation (HR: 2.20; P = 0.002), with an annualized event rate of 2.7%/year. A total of 39 (24%) patients reached the combined end point of SCD, stroke, or LV dysfunction (2.12%/y) with an HR of 1.47/cm increase in aneurysm size (P = 0.003) and an HR of 2.22 for patients with aneurysm size ≥2 cm (P = 0.02). CONCLUSIONS: Increasing aneurysm size confers poorer prognosis. Aneurysm size ≥2 cm should alert potential consideration for prophylactic anticoagulation and primary prevention ICDs.

Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy: Equivalent Detection by Magnetic Resonance Imaging and Contrast Echocardiography.

BACKGROUND: Left ventricular (LV) apical aneurysm is a unique morphological entity and novel adverse risk marker existing within the broad phenotypic spectrum of hypertrophic cardiomyopathy (HCM). Its true prevalence in the HCM population is likely underestimated because of inherent limitations of conventional noncontrast echocardiography. The authors hypothesized that contrast echocardiography is a reliable imaging technique compared with cardiovascular magnetic resonance (CMR) for the detection of apical aneurysms. The aim of this study was to assess the effectiveness of contrast echocardiography in the detection of LV apical aneurysms in patients with HCM in comparison with the gold standard, CMR. METHODS: One hundred twelve patients with HCM identified from an institutional clinical database, who underwent echocardiographic and CMR examinations within 12 months and had LV apical aneurysms identified on either or both imaging modalities, were retrospectively analyzed. Discordant cases were reviewed by an expert panel, and a consensus was reached regarding the presence or absence of an apical aneurysm. The reason for any discrepancy was recorded. RESULTS: The mean age of the patients was 59 ± 13 years, and 73% were men. Sixty-four (57%) underwent contrast echocardiography. The median interval between echocardiography and CMR was 118 days (interquartile range, 61-237 days). Thirty-nine patients (35%) had discordance between echocardiographic and CMR findings, of whom 20 had aneurysms reported on echocardiography but not CMR and 19 vice versa. Upon reanalysis by the expert panel, aneurysms were initially missed on CMR in 16 patients (80%), largely because of interpretation error secondary to small aneurysms, with a mean aneurysm size of 0.82 ± 0.38 cm in these cases. Before secondary review by the expert panel, contrast echocardiography had sensitivity of 97% compared with 85% for CMR (P = .0198) and 64% for noncontrast echocardiography (P = .0001). After secondary review, contrast echocardiography had sensitivity of 98% compared with 67% for noncontrast echocardiography (P = .0001) and 97% for CMR (P = 1.00). CONCLUSIONS: Contrast echocardiography has high sensitivity for detecting LV apical aneurysms and should be used routinely in the evaluation and risk stratification of patients with HCM.

An ascending aortic mass infected with Citrobacter koseri in a young woman.

BACKGROUND: Isolated aortic infection is rare and is typically associated with an underlying aortic aneurysm or a prosthetic aortic graft. CASE SUMMARY: A 38-year-old woman was admitted with symptoms of left upper limb ischaemia and had imaging findings suggestive of thrombus extending from the ascending aorta into the subclavian and brachial arteries. She underwent evacuation of the aortic masses and replacement of the ascending aorta. Citrobacter koseri was isolated from the excised tissue and the patient received 6 weeks of appropriate antibiotic therapy. DISCUSSION: This is an unusual case of acute upper limb ischaemia due to a mass infected with Citrobacter koseri in the ascending aorta without heart valve involvement.

A clinical enigma of ongoing constrictive pericarditis.

A 59-year-old lady presented with a 1-week history of orthopnoea, paroxysmal nocturnal dyspnoea, night sweats and a productive cough. She had no recent history of travel. Transthoracic echocardiogram revealed preserved left ventricular systolic function with abnormal pericardial thickening and restrictive left ventricular filling consistent with pericardial constriction. Cardiac magnetic resonance imaging confirmed a globally thickened pericardium and showed evidence of pericardial inflammation and constrictive physiology. She did not respond to diuresis, pulsed intravenous steroids or broad spectrum antibiotics and multiple investigations were negative, including autoimmune screen and tuberculosis cultures. Eventually a serum sample was found to be positive for Strongyloides stercoralis and it emerged that this lady had travelled to Egypt 8 years previously, where it is thought that she contracted S stercoralis leading to her developing constrictive pericarditis. This case report summarises the presentation and progression of this case and rare diagnosis.

An unusual presentation of pulmonary embolism.

Pulmonary embolism (PE) is a common cardiovascular emergency, by which occlusion of a part of the pulmonary arterial bed may lead to acute life threatening but potentially reversible right ventricular failure. Early diagnosis is fundamental to implement immediate effective treatment to reduce mortality. However, the diagnosis can be easily missed due to non-specific clinical presentation. We wish to present an unusual case whereby a patient with no risk factors for PE, symptoms suggestive of acute pericarditis and an ECG showing concave ST segment elevation was found to have multiple pulmonary emboli.