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The first confirmed case of novel Coronavirus Disease 2019 (COVID-19) in the United States was reported on January 20, 2020. As of November 24, 2020, close to 12.2 million cases of COVID-19 was confirmed in the US, with over 255,958 deaths. The rapid transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), its unusual and divergent presentation has strengthened the status of COVID-19 as a major public health threat. In this review, we aim to 1- discuss the epidemiological data from various COVID-19 patient cohorts around the world and the USA as well the associated risk factors; 2- summarize the pathophysiology of SARS-CoV-2 infection and the underlying molecular mechanisms for the respiratory and cardiovascular manifestations; 3- highlight the potential treatments and vaccines as well as current clinical trials for COVID-19., Graphical abstract Unlabelled Image, Highlights • COVID-19 represents a great threat to people's health worldwide with a high transmission rate and socioeconomic impacts. • Respiratory and cardiovascular conditions showed higher risks of complications and mortality of COVID-19 patients • Efficacy and safety of investigational drugs and other potential treatments for COVID-19.

Echocardiographic imaging is crucial for patient management during cardiotoxic cancer therapy. Left ventricular ejection fraction is the most commonly used parameter for identifying left ventricular dysfunction. However, it lacks sensitivity to detect subclinical changes in cardiac function due to cardiotoxic treatment. Global longitudinal strain (GLS) is the best studied strain parameter with established diagnostic and prognostic value. Multiple studies have demonstrated changes in GLS as an early marker of cardiotoxicity. This document serves as a primer to help clinicians in the acquisition and interpretation of strain in cardio-oncology. Cases with embedded videos illustrate a step-by-step approach to obtaining GLS measurements and common pitfalls to avoid. The document includes a concise summary of the indications of GLS in cardio-oncology and its role in guiding oncological therapy. Practical approaches on how to implement strain in the echo laboratory with guidance on training and quality assurance are also discussed., Central Illustration, Highlights • Compared with LVEF, GLS is a more sensitive and reproducible measure of LV systolic function and has emerged as an early marker of cardiotoxicity. • Despite evidence supporting the clinical utility of GLS imaging, familiarity with the practical process of strain imaging among clinicians is lacking. • Although each vendor has its own proprietary software for strain imaging, the basic steps of measuring GLS are similar. • Education is needed to enhance the performance, analysis, and interpretation of GLS for the management of cardio-oncology patients.

As our understanding of the complications of coronavirus disease–2019 (COVID-19) evolve, sub-clinical cardiac pathology such as myocarditis, pericarditis and right ventricular dysfunction in the absence of significant clinical symptoms represents a concern. The potential implications of these findings in athletes are significant given the concern that exercise, during the acute phase of viral myocarditis, may exacerbate myocardial injury and precipitate malignant ventricular arrhythmias. Such concerns have led to the development and publication of expert consensus documents aimed at providing guidance for the evaluation of athletes after contracting COVID-19 in order to permit safe return-to-play. Cardiac imaging is at the center of these evaluations. This review seeks to evaluate the current evidence regarding COVID-19associated cardiovascular disease and how multi-modality imaging may be useful in the screening and clinical evaluation of athletes with suspected cardiovascular complications of infection. Guidance is provided with diagnostic “red flags” that raise the suspicion of pathology. Specific emphasis is placed on the unique challenges posed in distinguishing athletic cardiac remodeling from sub-clinical cardiac disease. The strengths and limitations of different imaging modalities are discussed and an approach to return-to-play decision making for athletes’ post COVID-19, as informed by multi-modality imaging, is provided., Highlights: • COVID-19 may cause potential long-term cardiopulmonary complications in athletes, raising concern regarding return to play (RTP). • Exercise induced cardiac remodeling may be misinterpreted as COVID-19 related cardiac injury. • We discuss the strengths and limitations of relevant imaging modalities and an approach to RTP decision making. • Registry data of cardiac testing and outcomes in athletes after COVID-19 is needed to guide future screening strategies.

At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.

COVID-19 pandemic is causing delayed STEMI presentations associated with now unusual post-infarction complications. In this report we describe a delayed (5 days) STEMI presentation for the fear of contracting COVID-19 in the hospital. Patient suffered an extensive anterolateral STEMI complicated by subacute LVFWR that required a rapid surgical repair.

Cardiac diseases in the growing population of childhood cancer survivors are of major concern. Cardiotoxicity as a consequence of anthracyclines and chest radiotherapy continues to be relevant in the modern treatment era. Mitoxantrone has emerged as an important treatment-related risk factor and evidence on traditional cardiovascular risk factors in childhood cancer survivors is accumulating. International surveillance guidelines have been developed with the aim to detect and manage cardiac diseases early and prevent symptomatic disease. There is growing interest in risk prediction models to individualize prevention and surveillance. This State-of-the-Art Review summarizes literature from a systematic PubMed search focused on cardiac diseases after treatment for childhood cancer. Here, we discuss the prevalence, risk factors, prevention, risk prediction, and surveillance of cardiac diseases in survivors of childhood cancer., Central Illustration, Highlights • The main risk factors for cardiac disease in childhood cancer survivors are anthracyclines, mitoxantrone, and chest-directed radiotherapy dose. • Primary prevention strategies may reduce the risk of anthracycline-induced cardiomyopathy. • There is an increased prevalence of traditional cardiovascular risk factors in childhood cancer survivors; screening and early management are important to modify risk. • Multivariable risk prediction models may help to individualize prevention and surveillance strategies.

During the COVID-19 pandemic, we are likely to see a significant increase in the requests for rapid assessment of cardiac function, due to the frequent pre-existence of cardiac pathologies in patients admitted to hospital, and to the emergence of specific cardiac manifestations of this infection, such as myocarditis, sepsis related cardiomyopathy, stress induced cardiomyopathy and acute coronary syndromes. Hand-held, point-of-care ultrasound (HH-POCUS) is particularly suited for the provision of rapid, focused, integrated assessments of the heart and lungs. We present a review of the indications and protocols for focused HH-POCUS use in an acute setting and formulate proposals for streamlining their application in the COVID-19 context towards guiding optimum management of these patients while at the same time allowing adherence to robust infection control measures to provide safety to both the patient and our clinical staff.

A 18-year-old man without prior medical history developed fulminant myocarditis concomitant to severe COVID-19 pneumonia and confirmed by serial cardiac magnetic resonance. This may have important diagnostic, monitoring, and pathogenic implications., Graphical abstract

Background: Left ventricular (LV) pressure overload and coronary artery disease are common in patients with coarctation of aorta (COA), and they are risk factors for LV diastolic dysfunction. Patients with COA may have aortic vasculopathy that can result in LV pressure overload even in the absence of hemodynamically significant COA. We therefore hypothesized that patients with mild COA (without hemodynamically significant COA) will have more LV diastolic dysfunction compared to controls. Methods: Adult patients with mild COA (Doppler peak velocity 2 standard deviations above age-specific normative values) between adults with repaired COA and controls. Results: Of 204 COA and 204 control patients (age 35 ± 12 years), patients with COA had higher septal and lateral E/e′ ratio (12 ± 4 vs 9 ± 4, p = 0.009) and (10 ± 3 vs 7 ± 3, p 60 years (82% vs 56%, p = 0.076). Left ventricular mass index (LVMI) was the strongest determinant of E/e′ (β = 2.71 per 10 g/m2, standard error = 1.25, p

December 2019, a pathogenic novel human coronavirus (HCoV), termed SARS-CoV-2, was recognized in Wuhan, China causing significant morbidity and mortality. The illness caused by SARS-CoV-2 is labelled COVID-19 by WHO. We report the first case of COVID-19 in an ACHD patient with Single Ventricle (SV) physiology S/P Fontan palliation., Graphical abstract

Objective To evaluate cardiac involvement in recovered COVID-19 patients using cardiac MRI. Background Myocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19. Methods Twenty-six recovered COVID-19 patients that reported cardiac symptoms and underwent MRI exams were retrospectively included. MRI protocols consisted of conventional sequences (cine, T2WI, LGE), and quantitative mapping sequences (T1, T2, and ECV mapping). Edema ratio and LGE were assessed in post-COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls. Results Fifteen patients (58%) had abnormal MRI findings on conventional MRI sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased RV functional parameters including EF, CI, and SV/ BSA were found in patients with positive conventional MRI findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional MRI findings, compared to patients without positive findings and controls (median [IQR], native T1 1271ms [1243-1298] vs 1237ms [1216-1262] vs 1224ms [1217-1245]; mean [SD], T2 42.7ms [3.1] vs 38.1ms [2.4] vs 39.1ms [3.1]; median [IQR], 28.2% [24.8-36.2] vs 24.8% [23.1-25.4] vs 23.7% [22.2-25.2]; p=0.002, p, Graphical abstract

Highlights • Aortic dissection has a high mortality rate. It is common in elderly males. Aortic dilatation definitely increases risk but is not a must in every case. Clinical manifestation of Aortic dissection can be variable, therefore its diagnosis is challenging. • Primary suspicion of Aortic dissection is usually based on a patient’s history which varies from typical complaints like a sharp, severe tearing kind of backache with chest pain to asymptomatic until associated with valvular regurgitation. • Consequent treatment with antiplatelet, antithrombin and thrombolytic agents can cause life-threatening to bleed. Apart from good blood pressure control, prevention of aortic dissection can be done by elective aortic surgery in patients with dilated ascending aorta. • The most important and common risk factor is the systemic hypertension which has been reported in the 70% of the patients with aortic dissection. Most of the aortic dissection observed in young women has been reported to be related to pregnancy., Introduction Typically a patient with acute aortic dissection presents with severe chest pain radiating to the back, tearing in nature. Rarely it can present as painless acute aortic dissection this is seen in iatrogenic cases or when associated with atherosclerosis, diabetes, or aortic aneurysm. Case presentation We hereby present a case of a 32-year aged female who presented with dyspnoea & palpitations (NYHA III) from last 6 months, diagnosed to have Aortic Aneurysm with Type A dissection & Severe AR. She eventually underwent BENTALL’S procedure with CABG and had an uneventful recovery. Discussion Clinical manifestation of Aortic dissection can be variable, therefore its diagnosis is challenging. 25% of cases, may have associated ECG changes suggestive of acute coronary syndrome leading to a possible misdiagnosis especially if associated ST elevation in ECG. Aorto arteritis is a non-atherosclerotic chronic inflammatory vascular disease of unknown etiology that affects the aorta, proximal parts of its major branches. In this case, there is a possibility that there was underlying spontaneous coronary artery dissection which in turn could be cause for silent ischemia in young women. Conclusion Acute aortic dissection is a life-threatening disease with a high rate of cardiovascular morbidity and mortality. The most important and common risk factor is systemic hypertension which has been reported in the 70% of the patients with aortic dissection. Most of the aortic dissection observed in young women has been reported to be related to pregnancy. Dissection should be suspected during any acute coronary syndrome, particularly Inferior wall MI.

The coronavirus disease-2019 (COVID-19) is a global pandemic caused by the novel severe acute respiratory-syndrome coronavirus-2 that is resulting in substantial morbidity and mortality across the globe ([1][1]). Emerging data suggest that patients presenting with COVID-19 requiring hospitalization

Visual Abstract, Highlights • The new leadless pacemakers overcome important limitations of conventional devices but only provide single-chamber pacing capability. • The presented concept involves 2 leadless pacemakers that communicate wirelessly with each other and thus enable synchronized leadless dual-chamber pacing. • A novel technology is presented for pacemaker communication, using the myocardium and blood as the transmission medium. Optimal communication parameters were assessed in vivo and in vitro, and various features having an influence on signal transmission have been identified. • A leadless dual-chamber pacemaker prototype was developed and successfully tested in vivo. • The presented technique has shown to be a promising and energy-efficient wireless communication method for leadless dual-chamber pacemakers., Summary Contemporary leadless pacemakers only feature single-chamber pacing capability. This study presents a prototype of a leadless dual-chamber pacemaker. Highly energy-efficient intrabody communication was implemented for wireless pacemaker synchronization. Optimal communication parameters were obtained by in vivo and ex vivo measurements in the heart and blood. The prototype successfully performed dual-chamber pacing in vivo. The presented wireless communication method may in the future also enable leadless cardiac resynchronization therapy.

Background: Arterial hypertension adversely affects left atrial (LA) size and function, effect on function may precede effect on size. Many techniques were used to assess LA function but with pitfalls. Objectives: Early detection of left atrial dysfunction with speckle tracking echocardiography in hypertensive patients with normal left atrial size. Patients and methods: The study was conducted on 50 hypertensive patients and 50 age matched normotensive controls, all with normal LA volume index and free from any other cardiovascular disease that may affect the LA size or function. They were all subjected to history taking, clinical examination and echocardiographic study with assessment of LA functions [total LA stroke volume, LA expansion index by conventional 2D echocardiography and Global peak atrial longitudinal strain by speckle tracking (PALS)], left ventricular (LV) systolic and diastolic functions, and LV mass. Results: Different indices of LA dysfunction (Total LA stroke volume, LA expansion index and global PALS) were significantly lower in the hypertensive group despite the normal LA volume index in all the studied subjects. The presence of diabetes mellitus (DM) and higher grade of LV diastolic dysfunction were significantly associated with lower global PALS. The higher age, systolic blood pressure (BP), body mass index (BMI), LA volume index, and LV mass index and the lower LA expansion index were associated with lower global PALS. Conclusion: Speckle tracking echocardiography is a useful novel technique in detecting LA dysfunction in hypertension even before LA enlargement occurs. Keywords: Left atrium, Left atrial dysfunction, Hypertension, Speckle tracking

Objectives The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. Background AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. Methods This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro–brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Results In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro–brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). Conclusions CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471), Graphical abstract

Background: Mitral annular plane systolic excursion (MAPSE) is an M-mode derived echocardiographic marker of left ventricular longitudinal function, the aim of this study is to evaluate the value of MAPSE in assessment of contractile reserve in patients with ischemic cardiomyopathy before cardiac revascularization. Methods: The study included 50 patients with ischemic cardiomyopathy with ejection fraction (EF) ≤35%, the patients presented to echocardiography laboratory for dobutamine stress echocardiography (DSE) to assess viability and contractile reserve before revascularization, patients with primary valvular disease, and those with significant mitral annular calcifications were excluded from the study. A low dose DSE was done to all patients using standardized incremental infusions of 5, 10, and 20 μg/kg/min and the following parameters were measured at both baseline and peak dose, (EF, wall motion score index(WMSI) and MAPSE). Contractile reserve was measured as the difference between the low dose and baseline values of the EF and WMSI. Results: The study included 50 patients aged 55.08 ± 7.15 years, 94% were males, the DSE protocol was complete in all patients without serious side effects. A total of eight hundred segments were analyzed, at baseline 65% were dysfunctional including 31.2% hypokinetic, 28.8% were akinetic, and 5% were dyskinetic. At low dose study 70% of the dysfunctional myocardium showed viability, EF increased significantly from 30.84 ± 4.56 to 42.24 ± 8.15%, p 10% (AUC = 0.6, sensitivity 67.86, specificity 59.09), and Δ MAPSE ≥1.8 mm can predict contractile reserve at ΔWMSI ≤0.20 (AUC = 0.61, sensitivity 65.5, specificity 75.6). Conclusions: MAPSE is a rapid simple quantitative echocardiographic method that can asses contractile reserve in patients with ischemic cardiomyopathy before cardiac revascularization. Keywords: Mitral annulus systolic excursion, Contractile reserve, Ischemic cardiomyopathy

Visual Abstract, Highlights • Sunitinib, an oral tyrosine kinase inhibitor used widely to treat solid organ tumors, frequently induces hypertension and causes LV dysfunction in up to 19% of treated individuals. • Sunitinib-induced cardiotoxicity can be modeled using engineered CMT. • In CMT, sunitinib induces dose- and duration-dependent activation of apoptosis pathways and decreases in CMT force generation, spontaneous beating, and mitochondrial membrane potential. • Exposure of CMT to increased in vitro afterload intensifies the cardiotoxicity of clinically relevant sunitinib concentrations. • These findings suggest that intensive antihypertensive therapy may be an appropriate strategy to mitigate LV dysfunction observed in patients treated with sunitinib., Summary Sunitinib, a multitargeted oral tyrosine kinase inhibitor, used widely to treat solid tumors, results in hypertension in up to 47% and left ventricular dysfunction in up to 19% of treated individuals. The relative contribution of afterload toward inducing cardiac dysfunction with sunitinib treatment remains unknown. We created a preclinical model of sunitinib cardiotoxicity using engineered microtissues that exhibited cardiomyocyte death, decreases in force generation, and spontaneous beating at clinically relevant doses. Simulated increases in afterload augmented sunitinib cardiotoxicity in both rat and human microtissues, which suggest that antihypertensive therapy may be a strategy to prevent left ventricular dysfunction in patients treated with sunitinib.

Glutaredoxin 2 (GRX2), a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC) to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies., Graphical abstract fx1

Background: Aortic regurgitation (AR) usually occurs in diastole in presence of an incompetent aortic valve. Systolic AR is a rare phenomenon occurring in patients with reduced left ventricular systolic pressure and atrial fibrillation or premature ventricular contractions. Its occurrence is a Doppler peculiarity and adds to the hemodynamic burden. Aim: Rheumatic carditis is often characterised by acute or subacute severe mitral regurgitation (MR) due to flail anterior mitral leaflet and elongated chords. In patients with acute or subacute MR, developed left ventricular systolic pressure may fall in mid and late systole due to reduced afterload and end-systolic volume and may be lower than the aortic systolic pressure, causing flow reversal in aorta and systolic AR. Material and methods: 17 patients with acute rheumatic fever were studied in the echocardiography lab during the period 2005–2015. Five patients had severe MR of which two had no AR and hence were excluded from the study. Three young male patients (age 8–24 years) who met modified Jones’ criteria for rheumatic fever with mitral and aortic valve involvement were studied for the presence of systolic AR. Results: In presence of acute or subacute severe MR, flail anterior mitral valve and heart failure, all three showed both diastolic and late systolic AR by continuous-wave and color Doppler echocardiography. Conclusion: Systolic AR is a unique hemodynamic phenomenon in patients with acute rheumatic carditis involving both mitral and aortic valves and occurs in presence of severe MR. Keywords: Systolic aortic regurgitation, Reversed aorto-ventricular pressure gradient, Flail mitral valve

This case illustrates the potential for multiple cardiovascular complications in acute systemic lupus erythematous with antiphospholipid syndrome…, This case illustrates the potential for multiple cardiovascular complications in acute systemic lupus erythematous with antiphospholipid syndrome. (Level of Difficulty: Beginner.), Graphical abstract

The annual incidence of sudden cardiac death (SCD) in athletes is significantly lower than the general population. However, when SCD occurs in an athlete during sporting event or training, it sends shockwaves in the society and raises questions about cardiovascular effects of sports and exercise. This document reviews the causes and mechanism of SCD in sports and exercise in young and older athletes. In the Indian context, we suggest a 'pre-participation screening' of young and older athletes and consider a 'supervised, graded exercise regime' for the uninitiated, older sports participant. Finally, the document proposes medical infrastructure required to successfully revive a victim of sudden cardiac arrest during a sporting event.

Background Studies have shown regional and functional selectivity of cardiac postganglionic neurones indicating there might exist a similar heterogeneity in spinal segmental preganglionic neurones, which requires further investigation. Methods Right and left sympathetic chains were electrically stimulated from T6 to T1 in the innervated isolated rabbit heart preparation (n = 18). Sinus rate, left ventricular pressure, retrograde ventriculo-atrial conduction, monophasic action potential duration, effective refractory period, ventricular fibrillation threshold and electrical restitution were measured. Results Right sympathetic stimulation had a greater influence on heart rate (T1-T2: right; 59.9 ± 6.0%, left; 41.1 ± 5.6% P, Highlights • Direct evidence that the preganglionic sympathetic efferents show functionally distinct electrophysiological pathways in the rabbit heart • T1-T3 had a greater influence on heart rate and left ventricular pressure • T4-T6 of the left sympathetics had greater potential for arrhythmia generation

Background Myocardial fibrosis occurs in aortic stenosis (AS) as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in the form of increased mortality and morbidity. Objectives To assess the prevalence of LGE patterns using cardiac magnetic resonance (CMR) in severe AS patients and to study its prognostic significance. Methods Patients enrolled into the study from June 2012 to November 2014. All the patients underwent CMR and various patterns of LGE studied. These patients if symptomatic were advised AVR and others were managed conservatively. All patients were followed up and watched for outcomes like mortality, heart failure/hospitalization for cardiovascular cause, fall in left ventricular ejection fraction (LVEF) ≥20% and arrhythmia. Results A total of 109 patients (mean age-57.7 ± 12.5yrs) underwent CMR with 63 males. These patients were followed up for a mean of 13 months. Among 38 patients who underwent AVR, 6 died (5–cardiovascular cause, 1–non cardiovascular). 71 patients were managed conservatively out of which 18 died (17-cardiovascular cause, 1-non cardiovascular cause). LGE patterns were seen in 46 patients (43%); mid myocardial enhancement was seen in 31.1% of cases (33 patients). No LGE pattern was seen in 57%(63 patients). Basal and mid regions were maximally involved with mid myocardial enhancement in 66% & 68.3% respectively. LV ejection fraction (p = 0.002), peak aortic systolic velocity (p = 0.01) and peak aortic systolic gradient (p = 0.02) were the main predictors of LGE. Main predictors of primary outcome were NYHA class [OR- 13.4(2.8–26.1), p ≤ 0.001], age- 62 ± 9.6yrs(p = 0.001), EF simpson-50.9 ± 13%(p ≤ 0.001), LGE[OR 2.8 (1.27–6.47),p = 0.01], number of segments involved [2.37 ± 2.1,P ≤ 0.001] & CMR LV mass (151.73 ± 32 gms, p = 0.007). LGE predicted heart failure/hospitalization for cardiovascular cause [OR- 3.8(1.2–11.9), p = 0.01] and fall in LVEF [OR- 5.8(1.5–22.5), p = 0.005]. Patients with LGE had 2.87 times risk of adverse outcomes and patients with more than 3 segment LGE involvement had again increased chances for adverse outcomes. Conclusions LGE was detected by CMR in 43% of patients with severe AS. It predicted recurrent heart failure, hospitalization for cardiovascular cause and fall in LV ejection fraction. Our study has laid a path to larger prospective studies with long term follow up to assess the prognostic impact of CMR in patients with severe AS.

Visual Abstract, Highlights • Acellular ECM scaffolds retain bioactive properties capable of stimulating endogenous myocardial repair pathways that could be leveraged therapeutically to promote adaptive cardiac remodeling toward functional recovery after ischemic injury. • In rodents with MI, acellular bioactive ECM scaffolds surgically implanted on the epicardium stimulate adaptive cardiac repair and functional recovery with therapeutic effects highly dependent on the bioinductive properties of the biomaterial. • Interaction of human cardiac fibroblasts with bioactive ECM scaffolds can induce a robust FGF-dependent cell-mediated vasculogenic paracrine response capable of stimulating functional blood vessel assembly. • Acellular bioactive ECM scaffolds surgically implanted on the epicardium post-MI can reprogram resident fibroblasts and stimulate adaptive proreparative pathways enhancing functional recovery. • A novel surgical strategy for tissue repair is introduced that can be performed as an adjunct to conventional surgical revascularization with minimal translational challenges., Summary Structural cardiac remodeling after ischemic injury can induce a transition to heart failure from progressive loss of cardiac function. Cellular regenerative therapies are promising but face significant translational hurdles. Tissue extracellular matrix (ECM) holds the necessary environmental cues to stimulate cell-based endogenous myocardial repair pathways and promote adaptive remodeling toward functional recovery. Heart epicardium has emerged as an important anatomic niche for endogenous repair pathways including vasculogenesis and cardiogenesis. We show that acellular ECM scaffolds surgically implanted on the epicardium following myocardial infarction (MI) can attenuate structural cardiac remodeling and improve functional recovery. We assessed the efficacy of this strategy on post-MI functional recovery by comparing intact bioactive scaffolds with biologically inactivated ECM scaffolds. We confirm that bioactive properties within the acellular ECM biomaterial are essential for the observed functional benefits. We show that interaction of human cardiac fibroblasts with bioactive ECM can induce a robust cell-mediated vasculogenic paracrine response capable of functional blood vessel assembly. Fibroblast growth factor-2 is uncovered as a critical regulator of this novel bioinductive effect. Acellular bioactive ECM scaffolds surgically implanted on the epicardium post-MI can reprogram resident fibroblasts and stimulate adaptive pro-reparative pathways enhancing functional recovery. We introduce a novel surgical strategy for tissue repair that can be performed as an adjunct to conventional surgical revascularization with minimal translational challenges.

Congenitally corrected transposition of the great arteries is a rare heart defect that can be associated with systemic ventricular dysfunction and conduction disturbances. The use of cardiac resynchronization therapy in patients with congenital heart disease is not fully established, and achievement of successful pregnancies after implantation of transvenous, biventricular system has never been described, and which resulted in a significant clinical improvement. We describe a 33-year-old female with congenitally corrected transposition of the great arteries, who achieved six pregnancies and successful vaginal deliveries. The two last pregnancies were achieved after cardiac resynchronization therapy for systemic ventricular dysfunction and complete heart block. A congenital cardiac disease has been identified in only one offspring.