Role of open access echocardiography in detection of cardiac structural and functional abnormalities

PurposeTo evaluate the prevalence and incidence of significant structural heart disease in targeted patients with cardiac symptoms referred by general practitioners (GPs) using open access echocardiography, without prior clinical evaluation by a cardiologist.DesignData were derived from 488 subjects who underwent transthoracic echocardiography between January and April 2018. Patients were referred directly by GPs in East Berkshire, South England, through an online platform. Echocardiography was performed within 4–6 weeks of referral and all reports were assessed by a consultant cardiologist with expedited follow-up facilitated pro re nata. Results were analysed to determine the frequency of detection of structural abnormalities, particularly of the left ventricle and cardiac valves.ResultsEchocardiography was prospectively performed in consecutive subjects (50% male, mean (±SD) age 68.5±22 years; 50% female; mean (±SD) 64.6 (±19.1)). At least one abnormality likely to change management was found in 133 (27.3%) of all open access echocardiograms. Clinical heart failure with left ventricular systolic dysfunction (LVSD) and diastolic dysfunction was confirmed in 46 (9%) and 69 (14%), respectively. Of the 46 patients with LVSD, 33 were new diagnoses. Significant cardiac valve disease was found in 42 (8.6%) patients. 12 of these had known valvular disease or previous valvular surgery, and 30 were new diagnoses.ConclusionMajor structural and functional cardiac abnormalities are common in late middle-aged patients who present to GPs with cardiac symptoms and signs. Reported, unrestricted open access echocardiography enables early detection of significant cardiac pathology and timely intervention may improve cardiovascular outcomes.

Recent Advances in Modeling Mitochondrial Cardiomyopathy Using Human Induced Pluripotent Stem Cells

Around one third of patients with mitochondrial disorders develop a kind of cardiomyopathy. In these cases, severity is quite variable ranging from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. ATP is primarily generated in the mitochondrial respiratory chain via oxidative phosphorylation by utilizing fatty acids and carbohydrates. Genes in both the nuclear and the mitochondrial DNA encode components of this metabolic route and, although mutations in these genes are extremely rare, the risk to develop cardiac symptoms is significantly higher in this patient cohort. Additionally, infants with cardiovascular compromise in mitochondrial deficiency display a worse late survival compared to patients without cardiac symptoms. At this point, the mechanisms behind cardiac disease progression related to mitochondrial gene mutations are poorly understood and current therapies are unable to substantially restore the cardiac performance and to reduce the disease burden. Therefore, new strategies are needed to uncover the pathophysiological mechanisms and to identify new therapeutic options for mitochondrial cardiomyopathies. Here, human induced pluripotent stem cell (iPSC) technology has emerged to provide a suitable patient-specific model system by recapitulating major characteristics of the disease in vitro, as well as to offer a powerful platform for pre-clinical drug development and for the testing of novel therapeutic options. In the present review, we summarize recent advances in iPSC-based disease modeling of mitochondrial cardiomyopathies and explore the patho-mechanistic insights as well as new therapeutic approaches that were uncovered with this experimental platform. Further, we discuss the challenges and limitations of this technology and provide an overview of the latest techniques to promote metabolic and functional maturation of iPSC-derived cardiomyocytes that might be necessary for modeling of mitochondrial disorders.

Acute cardiac side effects after COVID-19 mRNA vaccination, a case series

Background: Since development and approval of the world´s first mRNA vaccines, created under pressure of the global pandemic caused by SARS-CoV-2, potential side effects have naturally been a much-debated topic. Vaccination may be one, if not the only way out of the pandemic claiming more than 4 million deaths worldwide to date. Potential side effects from vaccination have long been controversial, and case reports of fatal side effects have been published. Therefore, data are needed to identify persons being at high risk for potential side effects. Until September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© in young adults were registered by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©).Patients and Methods: Eight patients between 13-56 years of age, vaccinated with mRNA vaccine either BNT162b2 or mRNA-1273 between January and August 2021 developed cardiac side effects shortly after either their first or second vaccination. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after onset of symptoms and investigated further in severe cases. Symptoms were defined as dyspnea, chest pain, cardiac arrhythmia as determined by electrocardiography.Results: Eight patients (five males and three females) developed cardiac symptoms compatible with myocarditis according to CDC criteria shortly after SARS-CoV-2 mRNA vaccination. Three patients (two males, one female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within seven days after symptom onset Conclusion: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.

COVID-19 vs. Classical Myocarditis Associated Myocardial Injury Evaluated by Cardiac Magnetic Resonance and Endomyocardial Biopsy

Background: Despite the ongoing global pandemic, the impact of COVID-19 on cardiac structure and function is still not completely understood. Myocarditis is a rare but potentially serious complication of other viral infections with variable recovery, and is, in some cases, associated with long-term cardiac remodeling and functional impairment.Aim: To assess myocardial injury in patients who recently recovered from an acute SARS-CoV-2 infection with advanced cardiac magnetic resonance imaging (CMR) and endomyocardial biopsy (EMB).Methods: In total, 32 patients with persistent cardiac symptoms after a COVID-19 infection, 22 patients with acute classic myocarditis not related to COVID-19, and 16 healthy volunteers were included in this study and underwent a comprehensive baseline CMR scan. Of these, 10 patients post COVID-19 and 13 with non-COVID-19 myocarditis underwent a follow-up scan. In 10 of the post-COVID-19 and 15 of the non-COVID-19 patients with myocarditis endomyocardial biopsy (EMB) with histological, immunohistological, and molecular analysis was performed.Results: In total, 10 (31%) patients with COVID-19 showed evidence of myocardial injury, eight (25%) presented with myocardial oedema, eight (25%) exhibited global or regional systolic left ventricular (LV) dysfunction, and nine (28%) exhibited impaired right ventricular (RV) function. However, only three (9%) of COVID-19 patients fulfilled updated CMR–Lake Louise criteria (LLC) for acute myocarditis. Regarding EMB, none of the COVID-19 patients but 87% of the non-COVID-19 patients with myocarditis presented histological findings in keeping with acute or chronic inflammation. COVID-19 patients with severe disease on the WHO scale presented with reduced biventricular longitudinal function, increased RV mass, and longer native T1 times compared with those with only mild or moderate disease.Conclusions: In our cohort, CMR and EMB findings revealed that SARS-CoV-2 infection was associated with relatively mild but variable cardiac involvement. More symptomatic COVID-19 patients and those with higher clinical care demands were more likely to exhibit chronic inflammation and impaired cardiac function compared to patients with milder forms of the disease.

A rare combination of cardiovascular anomaly: Supravalvular aortic stenosis and congenital absence of right coronary artery

We reported a case of a 3-month-old infant presented with supravalvular aortic stenosis with congenital right coronary artery deficiency. According to cardiovascular CT results, Doty technique was adopted to restore the aortic root geometry under cardiopulmonary bypass. An angioplasty was performed to establish right coronary blood flow at the same time. The patient had no abnormal cardiac symptoms after surgery.

Case Report: Glucocorticoid Effect Observation in a Ureteral Urothelial Cancer Patient With ICI-Associated Myocarditis and Multiple Organ Injuries

Immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAEs) are becoming important safety issues worthy of attention despite the exciting therapeutic prospects. The growing development of new ICIs also brings new cases of irAEs, raising more challenges to clinicians. Cardiac injury is rare but life-threatening among diverse organ injuries, and effective interventions are critical for patients. Here, we report a novel programmed cell death protein-1 (PD-1) inhibitor tislelizumab-associated severe myocarditis and myositis accompanied by liver and kidney damage in a ureteral urothelial cancer patient, who was firstly treated by cardiologists because of cardiac symptoms. Due to the lack of experience about ICI-associated irAEs, an initial low-dose (0.5 mg/kg/day) and short-term methylprednisolone therapy was used and found to be ineffective and risky to the patient; then, steroid therapy was modulated to a higher dose (1.5 mg/kg/day) with prolonged time course, and improvement of patient symptoms and laboratory markers were observed quickly and persistently. The patient did not show adverse events under this steroid dosage. This case reports a rare tislelizumab-related myocarditis and multiple organ injuries, which provides valuable experience to cardiologists like us. Early recognition of ICI-associated myocarditis and sufficient dosage and time course of glucocorticoid therapy are critical for severe cases. High-quality clinical evidence about the precise diagnosis and therapy in ICI-associated myocarditis and other organ injuries are necessary to guide our clinical works.

Cardiovascular Risks Before Myocardial Infarction Differences Between Men and Women

Background Prodromal cardiac symptoms are warning signals preceding cardiac disease. Previous studies have shown some gender differences in prodromal symptoms as well as established risk factors for MI. This study aims to map possible gender differences in social factors and established risk factors preceding myocardial infarction (MI). Methods The study includes data of N=213 middle-aged men and women, all diagnosed with myocardial infarction (ICD-10 I21.9) from the region of south-east Sweden. They answered a questionnaire at discharge from the cardiologic clinic and additional clinical data from medical records were merged from the National Swedeheart Register. Results The dominant prodromal symptom for both sexes were experience of chest pain at the onset of MI. The major gender differences were that significantly more females (p=0.015) had a hyperlipidemia diagnose. Females also reported to have experienced higher stress load the year preceding myocardial infarction with serious life events (p=0.019), strained economy (p=0.003), and reports of sadness/depression (p<0.001). Females reported higher perceived stress load than men (p=0.006). Men had higher systolic blood pressure than women at hospital admission and a higher systolic- and diastolic blood pressure at discharge. Conclusion Influences of the social environment, such as serious life events, strained economy, depression, stress, and sleep deprivation were stronger as potential risk factors for myocardial infarction in women than among men. Of the traditional risk factors only, hyperlipidemia was more frequent among women. These findings could contribute to a deeper understanding of diagnostic differences between gender, as well as a more gender-oriented cardiovascular preventive work.

What an Interventionalist Needs to Know About INOCA

Ischaemia with non-obstructed coronary artery disease (INOCA) remains a diagnostic and therapeutic challenge. An anatomical investigation-based approach to ischaemic heart disease fails to account for disorders of vasomotion. The main INOCA endotypes are microvascular angina, vasospastic angina, mixed (both) or non-cardiac symptoms. The interventional diagnostic procedure (IDP) enables differentiation between clinical endotypes, with linked stratified medical therapy leading to a reduced symptom burden and a better quality of life. Interventionists are therefore well placed to make a positive impact with more personalised care. Despite adjunctive tests of coronary function being supported by contemporary guidelines, IDP use in daily practice remains limited. More widespread adoption should be encouraged. This article reviews a stratified approach to INOCA, describes a streamlined approach to the IDP and highlights some practical and safety considerations.

Early Myocardial Changes in Patients with Rheumatoid Arthritis without Known Cardiovascular Diseases—A Comprehensive Cardiac Magnetic Resonance Study

Clinically silent cardiac disease is frequently observed in rheumatoid arthritis (RA), and cardiovascular complications are the leading cause of mortality in RA. We sought to evaluate the myocardium of young RA patients without known cardiac disease using cardiac magnetic resonance (CMR), including T1/T2 mapping sequences. Eighteen RA patients (median age 41 years, 83% females) mainly with low disease activity or in remission and without any known cardiovascular disease were prospectively included to undergo CMR. A control group consisted of 10 sex- and age-matched patients without RA or any known structural cardiovascular disease. Heart chambers size and left/right ventricular systolic function were similar in patients with RA and controls. Signs of myocardial oedema were present in up to 39% of RA patients, including T2 time above cut-off value in 7 patients (39%) in comparison to none of the controls (p = 0.003) and T2 signal intensity ratio above the cut-off value in 6 patients (33%) and in none of the controls (p = 0.06). Extracellular volume was similar in both groups signifying a lack of diffuse fibrosis in studied group of RA patients. There were also no signs of late gadolinium enhancement (LGE) in either group except for one patient with RA who was found to have prior silent myocardial infarction. No correlation was found between markers of disease severity and markers of oedema observed on CMR in patients with RA. Nevertheless, patients with increased T2 time (≥50 ms) were more likely to have X-ray erosions (p = 0.02) and a longer duration between symptom onset and diagnosis (p = 0.02). Finally, there were no significant arrhythmias on 24-h ECG Holter monitoring in RA patients. CMR features of myocardial oedema without signs of myocardial fibrosis were found in 39% of young RA patients without known heart disease or cardiac symptoms. Presence of myocardial oedema was associated with X-ray erosions and a longer duration between symptom onset and diagnosis. The clinical significance of the observed early myocardial changes accompanying RA requires additional studies.

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

Cardiac alterations are frequently observed after acute neurological disorders. Takotsubo syndrome (TTS) represents an acute heart failure syndrome and is increasingly recognized as part of the spectrum of cardiac complications observed after neurological disorders. A systematic investigation of TTS patients with neurological disorders has not been conducted yet. The aim of the study was to expand insights regarding neurological disease entities triggering TTS and to investigate the clinical profile and outcomes of TTS patients after primary neurological disorders. The International Takotsubo Registry is an observational multicenter collaborative effort of 45 centers in 14 countries (ClinicalTrials.gov, identifier NCT01947621). All patients in the registry fulfilled International Takotsubo Diagnostic Criteria. For the present study, patients were included if complete information on acute neurological disorders were available. 2402 patients in whom complete information on acute neurological status were available were analyzed. In 161 patients (6.7%) an acute neurological disorder was identified as the preceding triggering factor. The most common neurological disorders were seizures, intracranial hemorrhage, and ischemic stroke. Time from neurological symptoms to TTS diagnosis was ≤ 2 days in 87.3% of cases. TTS patients with neurological disorders were younger, had a lower female predominance, fewer cardiac symptoms, lower left ventricular ejection fraction, and higher levels of cardiac biomarkers. TTS patients with neurological disorders had a 3.2-fold increased odds of in-hospital mortality compared to TTS patients without neurological disorders. In this large-scale study, 1 out of 15 TTS patients had an acute neurological condition as the underlying triggering factor. Our data emphasize that a wide spectrum of neurological diseases ranging from benign to life-threatening encompass TTS. The high rates of adverse events highlight the need for clinical awareness.