Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

QT Dispersion and Drug-Induced Torsade de Pointes.

Background Amiodarone causes less drug-induced torsade de pointes (TdP) compared to other class III antiarrhythmics. Two theories proposed for this finding include that amiodarone has less repolarization heterogeneity, and/or decreases early after depolarization (EADs). Corrected QT (QTc) dispersion as measured on a surface electrocardiogram (ECG) represents spatial heterogeneity of ventricular repolarization. Objective The purpose of this study was to analyze the difference in QT dispersion between amiodarone and other class III antiarrhythmics and to determine the etiology of TdP. Methods This was a retrospective, observational study at Montefiore Medical Center between January 2005 and January 2015. Inclusion criteria were adults >18 years on amiodarone, dofetilide, or sotalol with prolonged QT interval on 12-lead ECG. ECGs were reviewed by three blinded observers. QTc was calculated using the Bazett and Framingham formulas. QTc dispersion was calculated by subtracting the shortest from the longest QTc. Analysis of variance (ANOVA) was applied for comparison between antiarrhythmic groups with Bonferroni correction for multiple comparisons. Results A total of 447 ECGs were reviewed and 77 ECGs met inclusion criteria. The average QT dispersion for amiodarone, dofetilide, and sotalol was 0.050, 0.037, and 0.034, respectively (p=0.006) and the average QTc dispersion by Bazett was 0.053, 0.038, and 0.037 (p=0.008) and by Framingham was 0.049, 0.036, and 0.035 (p=0.009), respectively. Conclusion Our results show that given the increase in QT dispersion seen with amiodarone, heterogeneous ventricular repolarization as measured by QTc dispersion likely does not account for the lower incidence of drug-induced TdP seen with amiodarone. The ability of amiodarone to decrease EADs via sodium-channel blockade is more likely the explanation for its lower incidence of drug-induced TdP.

Association of human immunodeficiency virus and hepatitis C virus infection with long-term outcomes post-ST segment elevation myocardial infarction in a disadvantaged urban community.

BACKGROUND: HIV and HCV have been linked to an increased risk of cardiovascular disease (CVD). Their impact on long-term outcomes following ST-segment myocardial infarction (STEMI) has not been previously studied. METHODS: We leveraged data from a STEMI registry (n = 1208) at an inner-city health system to assess the influence of HIV and HCV on post-STEMI outcomes. Cox regression was used to compare HIV-monoinfected (n = 22), HCV-monoinfected (n = 26) and HIV-HCV-coinfected patients (n = 8) with the neither-infected group (n = 1152) with regard to death, death or any readmission, and death or CVD readmission. RESULTS: The cohort was majority black or Hispanic. Median follow-up was 4.3 years. Compared to the neither-infected group, the HIV-monoinfected group showed near-significantly higher risks of death or any readmission (HR = 1.62, 95% CI = 0.96, 2.74) and death or CVD readmission (HR = 1.82, 95% CI = 0.98, 3.39) after full adjustment. On similar comparison, the HCV-monoinfected group exhibited significantly higher risks of death (HR = 2.09, 95% CI = 1.05, 4.15) and death or any readmission (HR = 1.68, 95% CI = 1.07, 2.65), whereas the HIV-HCV-coinfected group showed higher risk of death (HR = 6.51, 95% CI = 2.28, 18.61). CONCLUSIONS: In this cohort composed mostly of race-ethnic minorities, HIV monoinfection tended to be associated with 1.6-to-1.8-fold higher risk of death or readmission for any cause or CVD over long-term follow-up compared to neither infection, whereas HCV monoinfection was associated with 1.7-to-2.1-fold higher risk of death and death or any readmission, and HIV-HCV coinfection with 6.5-fold higher risk of death. These associations require further study in larger populations, but highlight the importance of identifying and treating HIV and HCV in patients presenting with STEMI.

Mechanisms, pathophysiology, and diagnostic imaging of left ventricular outflow tract obstruction following mitral valve surgery and transcatheter mitral valve replacement.

Left ventricular outflow tract obstruction is a serious complication of mitral valve surgery (repair and replacement) and transcatheter mitral valve replacement. An appreciation of the various mechanisms which cause outflow obstruction in these settings is critical to avoiding this complication and to initiating appropriate treatment. This article discusses the mechanisms, pathophysiology, and imaging of left ventricular outflow tract obstruction which can arise following insertion of a variety of mitral valve prosthetics.

Malaligned bioprosthetic valve causing left ventricular outflow tract obstruction.

Left ventricular outflow tract obstruction resulting from strut impingement upon the interventricular septum is a rare complication of bioprosthetic mitral valve insertion. Obstruction is more likely to develop when a small, high profile prosthetic valve is inserted into a patient with a small outflow tract. The likelihood of this complication may be reduced by appropriate modification of surgical technique.

Transient Giant R Wave as a Marker for Ischemia in Unstable Angina.

Unstable angina is a clinical diagnosis that may present with or without electrocardiographic changes. The "giant R wave" on electrocardiogram has been reported as a manifestation of acute ischemia; however, it is a rare finding in current clinical practice. We describe a case of a patient with unstable angina and a transient "giant R wave" pattern with a culprit lesion in the right coronary artery.

Recurrent Stress Cardiomyopathy During COPD Exacerbation: Are Beta-adrenergic Agonists Only to Blame?

Takotsubo cardiomyopathy (TCM) is a variant of stress-induced cardiomyopathy, characterized by transient left ventricular dysfunction that may be associated with emotional or physical triggers. We present the case of a 51-year-old Caucasian female with severe chronic obstructive pulmonary disease (COPD) who presented with syncope and was found to have her second lifetime episode of stress-induced cardiomyopathy. Eight months prior, she had been admitted with a COPD exacerbation and was found to have left ventricular (LV) dysfunction with ejection fraction (EF) of 22% attributed to TCM with subsequent normalization of her left ventricular function. Recurrence of stress-induced cardiomyopathy associated with COPD is a rare phenomenon and its presentation raises the possibility of a common underlying mechanism.

Outcomes of ≤6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation: A meta-analysis and meta-regression.

BACKGROUND: The benefit of ≤6-month compared with 12-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) placement remains controversial. We performed a meta-analysis and meta-regression of ≤6-month versus 12-month DAPT in patients undergoing PCI with DES placement. METHODS: We conducted electronic database searches of randomized controlled trials (RCTs) comparing DAPT durations after DES placement. For studies with longer follow-up, outcomes at 12 months were identified. Odds ratios and 95% confidence intervals were computed with the Mantel-Haenszel method. Fixed-effect models were used; if heterogeneity (I) > 40 was identified, effects were obtained with random models. RESULTS: Nine RCTs were included with total n = 19,224 patients. No significant differences were observed between ≤6-month compared with 12-month DAPT in all-cause mortality (OR 0.87; 95% confidence interval (CI): 0.69-1.11), cardiovascular (CV) mortality (OR 0.89; 95% CI: 0.66-1.21), non-CV mortality (OR 0.85; 95% 0.58-1.24), myocardial infarction (OR 1.10; 95% CI: 0.89-1.37), stroke (OR 0.97; 95% CI: 0.67-1.42), stent thrombosis (ST) (OR 1.37; 95% CI: 0.89-2.10), and target vessel revascularization (OR 0.95; 95% CI: 0.77-1.18). No significant difference in major bleeding (OR 0.72; 95% CI: 0.49-1.05) was observed, though the all-bleeding event rate was significantly lower in the ≤6-month DAPT group (OR 0.76; 95% CI: 0.59-0.96). In the meta-regression analysis, a significant association between bleeding events and non-CV mortality with 12-month DAPT was found, as well as between ST and mortality in addition to MI with ≤6-month DAPT. CONCLUSION: DAPT for ≤6 months is associated with similar mortality and ischemic outcomes but less bleeding events compared with 12-month DAPT after PCI with DES.

Atrial Fibrillation Identified During Echocardiography in a Patient with Recurrent Cardioembolic Events: A Case Report.

BACKGROUND: Stroke is the major cause of disability and the fifth leading cause of death in the United States. In 30-40% of strokes the etiology remains uncertain or unknown. Identifying the cause of a cerebrovascular event offers the opportunity for an intervention that may decrease the risk of future stroke and thus prevent the resultant impairment. CASE REPORT: We report the case of an 80-year-old African American woman with a prior right middle cerebral artery stroke, who presented to the hospital with new left-sided weakness and was found to have a new right-sided frontal lobe infarct. Twenty-four hour Holter monitoring performed during this hospitalization and prior 24-h electrocardiogram (ECG) recording did not reveal an arrhythmia. However, the patient was found to have an isolated episode of atrial fibrillation (AF) during an echocardiogram as part of the evaluation for stroke etiology. CONCLUSIONS: AF is an important and treatable cause of recurrent stroke and needs to be ruled out by thorough evaluation before the diagnosis of cryptogenic stroke is assigned. Despite meticulous diagnostic work-up, many strokes caused by paroxysmal AF remain undetected and longer ECG monitoring (>24 h) may be required.

Thrombocytopaenia as a Prognostic Indicator in Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Studies suggest that thrombocytopaenia is associated with a higher mortality in several diseases. Little is known about the effect of low platelet count on mortality in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to determine the prognostic value of thrombocytopaenia in these patients by assessing all-cause mortality. METHODS: A total of 1,907 patients with HFrEF, defined by left ventricular ejection fraction <40% on echocardiography, were analysed in this multi-centre retrospective study. All patients were on medical therapy with a beta-blocker and an angiotensin-converting enzyme inhibitor. Patients were categorised into two groups based on platelet count measured within one month of the diagnosis of HFrEF: normal to mild thrombocytopaenia (platelet count 100,000-450,000 per uL); and moderate to severe thrombocytopaenia (platelet count <100,000 per uL). One-year all-cause mortality was compared between the two groups. RESULTS: Mean age was 65±15 years and 62% of patients were male. Overall one-year mortality was 17.2% with higher mortality among patients with HFrEF and moderate/severe thrombocytopaenia compared to those with normal/mild thrombocytopaenia (33.0% vs. 15.4%, p <0.001). After adjusting for baseline characteristics, patients with HFrEF and moderate/severe thrombocytopaenia had a higher mortality compared to patients with normal/mild thrombocytopaenia (HR 1.84, 95% CI 1.33-2.56, p <0.001). CONCLUSION: In patients with HFrEF, higher degree of thrombocytopaenia is associated with higher all-cause mortality. These findings may support the use of platelet counts as a prognostic marker in the assessment of the patient with HFrEF.

Clinical Profile, Acute Care, and Middle-Term Outcomes of Cocaine-Associated ST-Segment Elevation Myocardial Infarction in an Inner-City Community.

Although cocaine is a well-recognized risk factor for coronary disease, detailed information is lacking regarding related behavioral and clinical features of cocaine-associated ST-segment elevation myocardial infarction (STEMI), particularly in socioeconomically disadvantaged urban settings. Nor are systematic or extended follow-up data available on outcomes for cocaine-associated STEMI in the contemporary era of percutaneous coronary intervention. We leveraged a prospective STEMI registry from a large health system serving an inner-city community to characterize the clinical features, acute management, and middle-term outcomes of cocaine-related versus cocaine-unrelated STEMI. Of the 1,003 patients included, 60% were black or Hispanic. Compared with cocaine-unrelated STEMI, cocaine-related STEMI (n = 58) was associated with younger age, male gender, lower socioeconomic score, current smoking, high alcohol consumption, and human immunodeficiency virus seropositivity but less commonly with diabetes or hypertension. Cocaine users less often received drug-eluting stents or ß blockers at discharge. During median follow-up of 2.7 years, rates of death, death or any rehospitalization, and death or cardiovascular rehospitalization did not differ significantly between cocaine users and nonusers but were especially high for death or any hospitalization in the 2 groups (31.4 vs 32.4 per 100 person-years, p = 0.887). Adjusted hazard ratios for outcomes were likewise not significantly different. In conclusion, in this low-income community, cocaine use occurred in a substantial fraction of STEMI cases, who were younger than their nonuser counterparts but had more prevalent high-risk habits and exhibited similarly high rates of adverse outcomes. These data suggest that programs targeting cocaine abuse and related behaviors could contribute importantly to disease prevention in disadvantaged communities.

Patent foramen ovale: Unanswered questions.

The foramen ovale is a remnant of the fetal circulation that remains patent in 20-25% of the adult population. Although long overlooked as a potential pathway that could produce pathologic conditions, the presence of a patent foramen ovale (PFO) has been associated with a higher than expected frequency in a variety of clinical syndromes including cryptogenic stroke, migraines, sleep apnea, platypnea-orthodeoxia, deep sea diving associated decompression illness, and high altitude pulmonary edema. A unifying hypothesis is that a chemical or particulate matter from the venous circulation crosses the PFO conduit between the right and left atria to produce a variety of clinical syndromes. Although observational studies suggest a therapeutic benefit of PFO closure compared to medical therapy alone in patients with cryptogenic stroke, 3 randomized controlled trials (RCTs) did not confirm the superiority of PFO closure for the secondary prevention of stroke. However, meta-analyses of these RCTs demonstrate a significant benefit of PFO closure over medical therapy alone. Similarly, observational studies provide support for PFO closure for symptomatic relief of migraines. But one controversial randomized study failed to replicate the results of the observational studies while another two demonstrated a partial benefit. The goal of this review is to discuss the clinical conditions associated with PFO and provide internists and primary care physicians with current data on PFO trials, and clinical insight to help guide their patients who are found to have a PFO on echocardiographic testing.

The pathogenesis of cardiac fibrosis.

Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. This review discusses the cellular effectors and molecular pathways implicated in the pathogenesis of cardiac fibrosis. Although activated myofibroblasts are the main effector cells in the fibrotic heart, monocytes/macrophages, lymphocytes, mast cells, vascular cells and cardiomyocytes may also contribute to the fibrotic response by secreting key fibrogenic mediators. Inflammatory cytokines and chemokines, reactive oxygen species, mast cell-derived proteases, endothelin-1, the renin/angiotensin/aldosterone system, matricellular proteins, and growth factors (such as TGF-ß and PDGF) are some of the best-studied mediators implicated in cardiac fibrosis. Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible. Understanding the mechanisms responsible for initiation, progression, and resolution of cardiac fibrosis is crucial to design anti-fibrotic treatment strategies for patients with heart disease.

Lack of specificity of fibroblast-specific protein 1 in cardiac remodeling and fibrosis.

Understanding the role of fibroblasts in pathologic conditions is hampered by the absence of specific markers. Fibroblast-specific protein (FSP)1 has been suggested as a fibroblast-specific marker in normal and fibrotic tissues; FSP1 reporter mice and FSP1-Cre-driven gene deletion are considered reliable strategies to investigate fibroblast biology. Because fibroblasts are abundant in normal and injured mammalian hearts, we studied the identity of FSP1(+) cells in the infarcted and remodeling myocardium using mice with green fluorescent protein (GFP) expression driven by the FSP1 promoter. Neonatal and adult mouse hearts had low numbers of FSP1(+) cells. Myocardial infarction induced marked infiltration with FSP1-expressing cells that peaked after 72 h of reperfusion. Using flow cytometry, we identified 50% of FSP1(+) cells as hematopoietic cells; many endothelial cells were also FSP1(+). Increased infiltration with FSP1(+) cells was also noted in the pressure-overloaded myocardium. Although some FSP1(+) cells had fibroblast morphology, >30% were identified as hematopoietic cells, endothelial cells, or vascular smooth muscle cells. In contrast, periostin did not stain leukocytes or vascular cells but labeled spindle-shaped interstitial cells and, as a typical matricellular protein, was deposited in the matrix. CD11b(+) myeloid cells sorted from the infarcted heart had higher FSP1 expression than corresponding CD11b-negative cells, highlighting the predominant expression by hematopoietic cells. FSP1 is not a specific marker for fibroblasts in cardiac remodeling and fibrosis.

Targeting inflammatory pathways in myocardial infarction.

Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns (DAMPs), activating complement and Toll-Like Receptor (TLR)/Interleukin (IL)-1 signalling and triggering an intense inflammatory reaction. Infiltrating leucocytes clear the infarct from dead cells, while activating reparative pathways that lead to formation of a scar. As the infarct heals the ventricle remodels, the geometric, functional and molecular alterations associated with postinfarction remodelling are driven by the inflammatory cascade and are involved in the development of heart failure. Because unrestrained inflammation in the infarcted heart induces matrix degradation and cardiomyocyte apoptosis, timely suppression of the postinfarction inflammatory reaction may be crucial to protect the myocardium from dilative remodelling and progressive dysfunction. Inhibition and resolution of postinfarction inflammation involve mobilization of inhibitory mononuclear cell subsets and require activation of endogenous STOP signals. Our manuscript discusses the basic cellular and molecular events involved in initiation, activation and resolution of the postinfarction inflammatory response, focusing on identification of therapeutic targets. The failure of anti-integrin approaches in patients with myocardial infarction and a growing body of experimental evidence suggest that inflammation may not increase ischaemic cardiomyocyte death, but accentuates matrix degradation causing dilative remodelling. Given the pathophysiologic complexity of postinfarction remodelling, personalized biomarker-based approaches are needed to target patient subpopulations with dysregulated inflammatory and reparative responses. Inhibition of pro-inflammatory signals (such as IL-1 and monocyte chemoattractant protein-1) may be effective in patients with defective resolution of postinfarction inflammation who exhibit progressive dilative remodelling. In contrast, patients with predominant hypertrophic/fibrotic responses may benefit from anti-TGF strategies.

Systematic characterization of myocardial inflammation, repair, and remodeling in a mouse model of reperfused myocardial infarction.

Mouse models of myocardial infarction are essential tools for the study of cardiac injury, repair, and remodeling. Our current investigation establishes a systematic approach for quantitative evaluation of the inflammatory and reparative response, cardiac function, and geometry in a mouse model of reperfused myocardial infarction. Reperfused mouse infarcts exhibited marked induction of inflammatory cytokines that peaked after 6 hr of reperfusion. In the infarcted heart, scar contraction and chamber dilation continued for at least 28 days after reperfusion; infarct maturation was associated with marked thinning of the scar, accompanied by volume loss and rapid clearance of cellular elements. Echocardiographic measurements of end-diastolic dimensions correlated well with morphometric assessment of dilative remodeling in perfusion-fixed hearts. Hemodynamic monitoring was used to quantitatively assess systolic and diastolic function; the severity of diastolic dysfunction following myocardial infarction correlated with cardiomyocyte hypertrophy and infarct collagen content. Expression of molecular mediators of inflammation and cellular infiltration needs to be investigated during the first 72 hr, whereas assessment of dilative remodeling requires measurement of geometric parameters for at least four weeks after the acute event. Rapid initiation and resolution of the inflammatory response, accelerated scar maturation, and extensive infarct volume loss are important characteristics of infarct healing in mice.