COVID-19 and myocardial injury

The 2019 coronavirus pandemic (COVID-19), caused by SARS-CoV-2, has affected millions globally and has accounted for a multitude of deaths. Cardiovascular involvement with myocardial injury is common and is associated with severe morbidity and mortality. The pathophysiology of acute myocardial injury is complex and may include type I and type II myocardial infarction, direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to hypoxia. Angiotensin converting enzyme-2 receptors (ACE2-R) play a pivotal role in mediating viral entry into cells. Disruption of receptor signalling may also be the principal mechanism facilitating viral pathogenicity and altered ACE2-R biology may be a reason why patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and more likely to develop severe symptoms. New-onset hypertension, arrhythmia, myocarditis, heart failure, cardiomyopathy and coronary heart disease are among major cardiovascular disease comorbidities and complications seen in severe cases of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers, mainly cardiac troponins I and T, in the infected patients – especially those with severe disease. Myocarditis is another cause of morbidity among COVID-19 patients

Apical Hypertrophic Cardiomyopathy: The Variant Less Known

Hypertrophic cardiomyopathy (HCM) is an umbrella term for a heterogeneous heart muscle disease that was historically (and still is) defined by the detection of left ventricular (LV) hypertrophy (LVH) in the absence of abnormal cardiac loading conditions. Long after this morphological definition was established, the genetic basis of HCM was discovered, and we now know it is predominantly caused by autosomal dominant mutations in sarcomeric protein genes.1 Several patterns of LVH have been described in HCM: asymmetric septal (here referred to as “classic” HCM), concentric, reverse septal, neutral, and apical (ApHCM),2 as well as other, rarer LVH variants such as isolated lateral LVH and isolated inferoseptal LVH. Distinguishing between morphological HCM subtypes has conferred little in terms of personalized management strategies, with one distinctive exception: ApHCM. Compared with classic HCM, ApHCM is more sporadic, sarcomere mutations are detected less frequently, there is more atrial fibrillation (AF) and sudden cardiac death (SCD) risk factors differ. No authoritative ApHCM‐specific recommendations to guide diagnosis, family screening, and patient risk stratification currently exist. First described in Japan in 1976,2 ApHCM is exemplified by “giant” negative precordial T‐waves on electrocardiography and by “spadelike” configuration of its LV cavity in end diastole.3 This review summarizes the epidemiology, clinical expression, genetics, and prognosis of ApHCM, while also highlighting knowledge gap

Therapeutic benefits of distal ventricular pacing in mid-cavity obstructive hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms. METHODS: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed. RESULTS: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: -70.86 to -40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: -37.19 to -13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure (p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) (n = 5), phrenic nerve stimulation (n = 3) and ventricular ectopy (n = 1). CONCLUSION: In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration

Diagnostic Impact of Repeated Expert Review & Long‐Term Follow‐Up in Determining Etiology of Idiopathic Cardiac Arrest

Background: Recognizing the etiology of sudden cardiac arrest (SCA) has an enormous impact on the management of victims and their immediate families. A significant proportion of SCA survivors with a structurally normal heart are not offered a diagnosis and there is no clear consensus on the type and duration of follow‐up. We aimed to assess the utility of a multidisciplinary approach in optimizing diagnosis of cardiac arrest etiology during follow‐up. Methods and Results: We retrospectively assessed 327 consecutive SCA survivors (mean age 61.9±16.2 years, 80% men) who underwent secondary prevention implantable cardioverter defibrillators between May 2015 and November 2018. The initial diagnosis was recorded at the time of admission and follow‐up diagnosis was deduced from subsequent clinic records, investigations, and outcomes of multidisciplinary team meetings. Structural heart disease accounted for 282 (86%) of SCAs. Forty‐five (14%) patients had a structurally normal heart and underwent comprehensive testing and follow‐up (mean duration 93±52 weeks). On initial evaluation, 14/45 (31%) of these received a diagnosis, rising to 29/45 (64%) with serial reviews during follow‐up. Discussion in multidisciplinary team meetings and imaging reassessment accounted for 47% of new diagnoses. No additional diagnoses were made beyond 96 weeks. Nineteen (5.8%) fatalities occurred in the entire cohort, exclusively in patients with structural heart disease. Conclusions: Systematic comprehensive testing combined with multidisciplinary expert team review of SCA survivors without structural heart disease improves the yield and time to diagnosis compared with previously published studies. This approach has positive implications in the management of SCA survivors and their families

Characterizing the hypertensive cardiovascular phenotype in the UK Biobank

Aims: To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations. Methods and results: We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control. Conclusion: Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control

The atrial and ventricular myocardial proteome of endstage lamin heart disease

Lamins A/C (encoded by LMNA gene) can lead to dilated cardiomyopathy (DCM). This pilot study sought to explore the postgenomic phenotype of end-stage lamin heart disease. Consecutive patients with end-stage lamin heart disease (LMNA-group, n = 7) and ischaemic DCM (ICM-group, n = 7) undergoing heart transplantation were prospectively enrolled. Samples were obtained from left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV) and interventricular septum (IVS), avoiding the infarcted myocardial segments in the ICM-group. Samples were analysed using a discovery 'shotgun' proteomics approach. We found that 990 proteins were differentially abundant between LMNA and ICM samples with the LA being most perturbed (16-fold more than the LV). Abundance of lamin A/C protein was reduced, but lamin B increased in LMNA LA/RA tissue compared to ICM, but not in LV/RV. Carbonic anhydrase 3 (CA3) was over-abundant across all LMNA tissue samples (LA, LV, RA, RV, and IVS) when compared to ICM. Transthyretin was more abundant in the LV/RV of LMNA compared to ICM, while sarcomeric proteins such as titin and cardiac alpha-cardiac myosin heavy chain were generally less abundant in RA/LA of LMNA. Protein expression profiling and enrichment analysis pointed towards sarcopenia, extracellular matrix remodeling, deficient myocardial energetics, redox imbalances, and abnormal calcium handling in LMNA samples. Compared to ICM, end-stage lamin heart disease is a biventricular but especially a biatrial disease appearing to have an abundance of lamin B, CA3 and transthyretin, potentially hinting to compensatory responses

Catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a European observational multicentre study

AIMS: Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM). Data on the efficacy of catheter ablation of AF in HCM patients are sparse. METHODS AND RESULTS: Observational multicentre study in 137 HCM patients (mean age 55.0 ± 13.4, 29.1% female; 225 ablation procedures). We investigated (i) the efficacy of catheter ablation for AF beyond the initial 12 months; (ii) the available risk scores, stratification schemes and genotype as potential predictors of arrhythmia relapse, and (iii) the impact of cryoballoon vs. radiofrequency in procedural outcomes. Mean follow-up was 43.8 ± 37.0 months. Recurrences after the initial 12-month period post-ablation were frequent, and 24 months after the index procedure, nearly all patients with persistent AF had relapsed, and only 40% of those with paroxysmal AF remained free from arrhythmia recurrence. The APPLE score demonstrated a modest discriminative capacity for AF relapse post-ablation (c-statistic 0.63, 95% CI 0.52-0.75; P = 0.022), while the risk stratification schemes for sudden death did not. On multivariable analysis, left atrium diameter and LV apical aneurysm were independent predictors of recurrence. Fifty-eight patients were genotyped; arrhythmia-free survival was similar among subjects with different gene mutations. Rate of procedural complications was high (9.3%), although reducing over time. Outcome for cryoballoon and radiofrequency ablation was comparable. CONCLUSION: Very late AF relapses post-ablation is common in HCM patients, especially in those with persistent AF. Left atrium size, LV apical aneurysm, and the APPLE score might contribute to identify subjects at higher risk of arrhythmia recurrence. First-time cryoballoon is comparable with radiofrequency ablation

Ineffective and prolonged apical contraction is associated with chest pain and ischaemia in apical hypertrophic cardiomyopathy.

OBJECTIVES: To investigate the hypothesis that persistence of apical contraction into diastole is linked to reduced myocardial perfusion and chest pain. BACKGROUND: Apical hypertrophic cardiomyopathy (HCM) is defined by left ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic contractility resulting in obliteration of the apical cavity is often present. Apical HCM can lead to drug-refractory chest pain. METHODS: We retrospectively studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi), late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional contractile persistence (apex, mid and basal LV). RESULTS: In apical HCM, apical MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration of contractile persistence was associated with lower MPRi (p<0.01) and chest pain (p<0.05). In multivariate regression, contractile persistence was independently associated with chest pain (p<0.01) and reduced MPRi (p<0.001). CONCLUSION: In apical HCM, regional contractile persistence is associated with impaired myocardial perfusion and chest pain. As apical myocardium makes limited contributions to stroke volume, apical contractility is also largely ineffective. Interventions to reduce apical contraction and/or muscle mass are potential therapies for improving symptoms without reducing cardiac output.FP and SEP acknowledge the National Institute for Health Research (NIHR) Cardiovascular Biomedical Research Centre at Barts. FP has received grant support from Siemens Healthcare