Sex-based differences in the phenotypic expression and prognosis of idiopathic non-ischaemic cardiomyopathy: a cardiovascular magnetic resonance study.

AIMS: We sought to characterize sex-related differences in cardiovascular magnetic resonance-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia. A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; P < 0.01 for all) vs. males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (22% vs. 34%; P < 0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; P = 0.003 and 0.005). There was no association of sex with the outcome. CONCLUSION: In a large contemporary cohort, NICM was uniquely expressed in females vs. males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.

Natural History of Myocardial Injury After COVID-19 Vaccine-Associated Myocarditis.

BACKGROUND: Acute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. Little is known about the natural history of this complication. METHODS: Baseline and convalescent (≥ 90 days) cardiac magnetic resonance (CMR) imaging assessments were performed in 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination. CMR-based changes in left ventricular volumes, mass, ejection fraction (LVEF), markers of tissue inflammation (native T1 and T2 mapping), and fibrosis (late gadolinium enhancement [LGE] and extracellular volume [ECV]) were assessed between baseline and convalescence. Cardiac symptoms and clinical outcomes were captured. RESULTS: Median age was 23.1 years (range 18-39 years), and 17 (85%) were male. Convalescent evaluations were performed at a median (IQR) 3.7 (3.3-6.2) months. The LVEF showed a mean 3% absolute improvement, accompanied by a 7% reduction in LV end-diastolic volume and 5% reduction in LV mass (all P < 0.015). Global LGE burden was reduced by 66% (P < 0.001). Absolute reductions in global T2, native T1, and ECV of 2.1 ms, 58 ms, and 2.9%, repectively, were documented (all P ≤ 0.001). Of 5 patients demonstrating LVEF ≤ 50% at baseline, all recovered to above this threshold in convalescence. A total of 18 (90%) patients showed persistence of abnormal LGE although mean fibrosis burden was < 5% of LV mass in 85% of cases. No patient experienced major clinical outcomes. CONCLUSIONS: COVID-19 mRNA vaccine-associated myocarditis showed rapid improvements in CMR-based markers of edema, contractile function, and global LGE burden beyond 3 months of recovery in this young patient cohort. However, regional fibrosis following edema resolution was commonly observed, justifying need for ongoing surveillance.

Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.

AIMS: We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site. METHODS AND RESULTS: We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%). CONCLUSION: We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.

Mid-wall striae fibrosis predicts heart failure admission, composite heart failure events, and life-threatening arrhythmias in dilated cardiomyopathy.

Heart failure (HF) admission is a dominant contributor to morbidity and healthcare costs in dilated cardiomyopathy (DCM). Mid-wall striae (MWS) fibrosis by late gadolinium enhancement (LGE) imaging has been associated with elevated arrhythmia risk. However, its capacity to predict HF-specific outcomes is poorly defined. We investigated its role to predict HF admission and relevant secondary outcomes in a large cohort of DCM patients. 719 patients referred for LGE MRI assessment of DCM were enrolled and followed for clinical events. Standardized image analyses and interpretations were conducted inclusive of coding the presence and patterns of fibrosis observed by LGE imaging. The primary clinical outcome was hospital admission for decompensated HF. Secondary heart failure and arrhythmic composite endpoints were also studied. Median age was 57 (IQR 47-65) years and median LVEF 40% (IQR 29-47%). Any fibrosis was observed in 228 patients (32%) with MWS fibrosis pattern present in 178 (25%). At a median follow up of 1044 days, 104 (15%) patients experienced the primary outcome, and 127 (18%) the secondary outcome. MWS was associated with a 2.14-fold risk of the primary outcome, 2.15-fold risk of the secondary HF outcome, and 2.23-fold risk of the secondary arrhythmic outcome. Multivariable analysis adjusting for all relevant covariates, inclusive of LVEF, showed patients with MWS fibrosis to experience a 1.65-fold increased risk (95% CI 1.11-2.47) of HF admission and 1-year event rate of 12% versus 7% without this phenotypic marker. Similar findings were observed for the secondary outcomes. Patients with LVEF > 35% plus MWS fibrosis experienced similar event rates to those with LVEF ≤ 35%. MWS fibrosis is a powerful and independent predictor of clinical outcomes in patients with DCM, identifying patients with LVEF > 35% who experience similar event rates to those with LVEF below this conventionally employed high-risk phenotype threshold.

Impact of cancer diagnosis on causes and outcomes of 5.9 million US patients with cardiovascular admissions.

INTRODUCTION: There are limited data on causes of cardiovascular (CV) admissions and associated outcomes among patients with different cancers. METHODS: All CV admissions from the US National Inpatient Sample between October 2015 to December 2017 were stratified by cancer type as well as metastatic status. Multivariable logistic regression was performed to determine the adjusted odds ratios (aOR) of in-hospital mortality in different groups. RESULTS: From 5,936,014 eligible CV admissions, cancer was present in 265,221 (4.5%) hospitalizations. There was significant variation in the admission diagnoses among the different cancers, with hematological malignancies being principally associated with heart failure (HF), lung cancer with atrial fibrillation (AF), and colorectal and prostate cancer with acute myocardial infarction (AMI). Admission with haemorrhagic stroke has the highest associated mortality across cancers (20.0-38.4%). In-hospital mortality was higher in cancer than non-cancer patients across most CV admissions (P < 0.001) with AF having the worst prognosis. Compared to group without any cancer, the greatest aOR of mortality was associated with lung cancer in AMI (aOR 2.32, 95% CI 2.18-2.47), ischemic stroke (aOR 2.21, 95%CI 2.08-2.34), AF (aOR 4.69, 95%CI 4.32-5.10) and HF (aOR 2.07, 95%CI 1.89-2.27). CONCLUSIONS: The most common causes of CV admission to hospital vary in patients with different types of cancer, with AMI being most common in patients with colon cancer, HF in patients with hematological malignancies and AF in patients with lung cancer. Patients with cancer, particularly lung cancer, have greater mortality than non-cancer patients after admissions with a CV cause.

Effect of Active Cancer on the Cardiac Phenotype: A Cardiac Magnetic Resonance Imaging-Based Study of Myocardial Tissue Health and Deformation in Patients With Chemotherapy-Naïve Cancer.

Background The overlap between cancer and cardiovascular care continues to expand, with intersections emerging before, during, and following cancer therapies. To date, emphasis has been placed on how cancer therapeutics influence downstream cardiac health. However, whether active malignancy itself influences chamber volumes, function, or overall myocardial tissue health remains uncertain. We sought to perform a comprehensive cardiovascular magnetic resonance-based evaluation of cardiac health in patients with chemotherapy-naïve cancer with comparison with a healthy volunteer population. Methods and Results Three-hundred and eighty-one patients with active breast cancer or lymphoma before cardiotoxic chemotherapy exposure were recruited in addition to 102 healthy volunteers. Both cohorts underwent standardized cardiovascular magnetic resonance imaging with quantification of chamber volumes, ejection fraction, and native myocardial T1. Left ventricular mechanics were incrementally assessed using three-dimensional myocardial deformation analysis, providing global longitudinal, circumferential, radial, and principal peak-systolic strain amplitude and systolic strain rate. The mean age of patients with cancer was 53.8±13.4 years; 79% being women. Despite similar left ventricular ejection fraction, patients with cancer showed smaller chambers, increased strain amplitude, and systolic strain rate in both conventional and principal directions, and elevated native T1 versus sex-matched healthy volunteers. Adjusting for age, sex, hypertension, and diabetes mellitus, the presence of cancer remained associated with these cardiovascular magnetic resonance parameters. Conclusions The presence of cancer is independently associated with alterations in cardiac chamber size, function, and objective markers of tissue health. Dedicated research is warranted to elucidate pathophysiologic mechanisms underlying these findings and to explore their relevance to the management of patients with cancer referred for cardiotoxic therapies.

Contribution of mitral valve leaflet length and septal wall thickness to outflow tract obstruction in patients with hypertrophic cardiomyopathy.

We sought to examine whether elongation of the mitral valve leaflets in patients with hypertrophic cardiomyopathy (HCM) is synergistic to septal wall thickness (SWT) in the development of left ventricular outflow tract obstruction (LVOTO). HCM is a common genetic cardiac disease characterized by asymmetric septal hypertrophy and predisposition towards LVOTO. It has been reported that elongation of the mitral valve leaflets may be a primary phenotypic feature and contribute to LVOTO. However, the relative contribution of this finding versus SWT has not been studied. 152 patients (76 with HCM and 76 non-diseased age, race and BSA-matched controls) and 18 young, healthy volunteers were studied. SWT and the anterior mitral valve leaflet length (AMVLL) were measured using cine MRI. The combined contribution of these variables (SWT × AMVLL) was described as the Septal Anterior Leaflet Product (SALP). Peak LVOT pressure gradient was determined by Doppler interrogation and defined as "obstructive" if ≥ 30 mmHg. Patients with HCM were confirmed to have increased AMVLL compared with controls and volunteers (p < 0.01). Among HCM patients, both SWT and SALP were significantly higher in patients with LVOTO (N = 17) versus without. SALP showed modest improvement in predictive accuracy for LVOTO (AUC = 0.81) among the HCM population versus SWT alone (AUC = 0.77). However, in isolated patients this variable identified patients with LVOTO despite modest SWT. Elongation of the AMVLL is a primary phenotypic feature of HCM. While incremental contributions to LVOTO appear modest at a population level, specific patients may have dominant contribution to LVOTO. The combined marker of SALP allows for maintained identification of such patients despite modest increases in SWT.

Phenotypic analysis of arrhythmogenic cardiomyopathy in the Hutterite population: role of electrocardiogram in identifying high-risk desmocollin-2 carriers.

BACKGROUND: The p.Gln554X mutation in desmocollin-2 (DSC2) is prevalent in ≈10% of the Hutterite population. While the homozygous mutation causes severe biventricular arrhythmogenic right ventricular cardiomyopathy, the phenotypic features and prognosis of heterozygotes remain incompletely understood. METHODS AND RESULTS: Eleven homozygotes (mean age 32±8 years, 45% female), 28 heterozygotes (mean age 40±15 years, 50% female), and 22 mutation-negatives (mean age 43±17 years, 41% female) were examined. Diagnostic testing was performed as per the arrhythmogenic right ventricular cardiomyopathy modified Task Force Criteria. Inverted T waves in the right precordial leads on ECG were seen in all homozygotes but not in their counterparts (P<0.001). Homozygotes had higher median daily premature ventricular complex burden than did heterozygotes or mutation-negatives (1407 [IQR 1080 to 2936] versus 2 [IQR 0 to 6] versus 6 [IQR 0 to 214], P=0.0002). Ventricular tachycardia was observed in 60% of homozygotes but in none of the remaining individuals (P<0.001). On cardiac magnetic resonance imaging, homozygotes had significantly larger indexed end-diastolic volumes (right ventricular: 122±24 versus 83±17 versus 83±12 mL/m(2), P<0.0001; left ventricular: 93±18 versus 76±13 versus 80±11 mL/m(2), P=0.0124) and lower ejection fraction values compared with heterozygotes and mutation-negatives (right ventricular ejection fraction: 41±9% versus 59±9% versus 61±6%, P<0.0001; left ventricular ejection fraction: 53±8% versus 65±5% versus 64±5%, P<0.0001). Most affected individuals lacked right ventricular wall motion abnormalities. Thus, few met cardiac magnetic resonance imaging task force criteria. CONCLUSIONS: The ECG reliably identifies homozygous p.Gln554X carriers and may be useful as an initial step in the screening of high-risk Hutterites. The cardiac phenotype of heterozygotes appears benign, but further prospective follow-up of their arrhythmic risk is needed.

Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy.

BACKGROUND: The presence and extent of late gadolinium enhancement (LGE) has been associated with adverse events in patients with hypertrophic cardiomyopathy (HCM). Signal intensity (SI) threshold techniques are routinely employed for quantification; Full-Width at Half-Maximum (FWHM) techniques are suggested to provide greater reproducibility than Signal Threshold versus Reference Mean (STRM) techniques, however the accuracy of these approaches versus the manual assignment of optimal SI thresholds has not been studied. In this study, we compared all known semi-automated LGE quantification techniques for accuracy and reproducibility among patients with HCM. METHODS: Seventy-six HCM patients (51 male, age 54 ± 13 years) were studied. Total LGE volume was quantified using 7 semi-automated techniques and compared to expert manual adjustment of the SI threshold to achieve optimal segmentation. Techniques tested included STRM based thresholds of >2, 3, 4, 5 and 6 SD above mean SI of reference myocardium, the FWHM technique, and the Otsu-auto-threshold (OAT) technique. The SI threshold chosen by each technique was recorded for all slices. Bland-Altman analysis and intra-class correlation coefficients (ICC) were reported for each semi-automated technique versus expert, manually adjusted LGE segmentation. Intra- and inter-observer reproducibility assessments were also performed. RESULTS: Fifty-two of 76 (68%) patients showed LGE on a total of 202 slices. For accuracy, the STRM >3SD technique showed the greatest agreement with manual segmentation (ICC = 0.97, mean difference and 95% limits of agreement = 1.6 ± 10.7 g) while STRM >6SD, >5SD, 4SD and FWHM techniques systematically underestimated total LGE volume. Slice based analysis of selected SI thresholds similarly showed the STRM >3SD threshold to most closely approximate manually adjusted SI thresholds (ICC = 0.88). For reproducibility, the intra- and inter-observer reproducibility of the >3SD threshold demonstrated an acceptable mean difference and 95% limits of agreement of -0.5 ± 6.8 g and -0.9 ± 5.6 g, respectively. CONCLUSIONS: FWHM segmentation provides superior reproducibility, however systematically underestimates total LGE volume compared to manual segmentation in patients with HCM. The STRM >3SD technique provides the greatest accuracy while retaining acceptable reproducibility and may therefore be a preferred approach for LGE quantification in this population.

Psychological distress in cardiac rehabilitation participants.

PURPOSE: Limited data are available on the psychosocial characteristics of patients entering cardiac rehabilitation (CR). We characterized the psychological and clinical profiles of men and women entering CR to determine which, if any, characteristic identifies persons at high risk for psychological distress. METHODS: The records of 417 patients enrolled in phase II CR between January 2001 and December 2004 were analyzed. One hundred forty-eight of these patients underwent a comprehensive Symptom Checklist-90 psychological survey. The analysis focused on measures of depression, anxiety, hostility, somatization, and a global severity index. RESULTS: Mean age of the patients was 60.6 years and 20.9% of them were women. More than one-third had a score of 90th percentile or more in at least 1 psychological category, and 23% had a score of 90th percentile or more in 3 or more categories. Approximately 20% and 36% of patients scoring in the 90th percentile or more and 98th percentile or more of depressive symptoms, respectively, had a history of depression. There was no difference in Symptom Checklist-90 scores by gender, age, education, work status, type of coronary event, metabolic syndrome, tobacco use, cerebrovascular disease, peripheral vascular disease, or diabetes. There was no relationship between psychological symptoms and indication for CR, although a trend of more somatic symptoms was seen in those who underwent an acute coronary syndrome and did not receive revascularization. CONCLUSION: Considering the prevalence of psychological distress in CR patients and the lack of clinical identifiers, routine assessment could help identify those who are at increased risk of noncompliance and may benefit from psychological and/or pharmacological intervention.

Prognostic value of admission fasting glucose levels in patients with acute coronary syndrome.

Data are limited regarding the best prognostic glucose measure for patients admitted for an acute coronary event. We examined the admission fasting glucose levels among patients with acute coronary syndrome (ACS) from the University of Michigan ACS registry. The glucose levels were grouped into 3 categories (> or =70 to <100, 100 to <126, and > or =126 mg/dl). The primary outcome measures included mortality and a composite end point (stroke, recurrent infarction, and death) in hospital and at 6 months after the ACS event. Of the 1,525 patients (29% with diabetes) for whom glucose levels were available, a fasting glucose level of > or =100 mg/dl was associated with increased in-hospital mortality, after adjusting for the Global Registry of Acute Coronary Events risk score and gender. A fasting glucose level of > or =126 mg/dl in patients with no known history of diabetes was associated with in-hospital adverse events (odds ratio 3.37, 95% confidence interval 1.51 to 7.51). The fasting glucose level was associated with an increased risk of 6-month mortality among nondiabetics (odds ratio 3.03, 95% confidence interval 1.35 to 6.81 for patients with a glucose level of 100 to 125 mg/dl; and odds ratio 2.81, 95% confidence interval 1.07 to 7.36 for patients with a glucose level of > or =126 mg/dl) but not for diabetic patients. In conclusion, we observed a strong association between the admission fasting glucose level and mortality, particularly among nondiabetic patients. Whether improving the diagnosis and treatment of hyperglycemia would result in reductions in adverse events after ACS remains unclear.

Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy.

STUDY OBJECTIVES: To characterize the safety of concomitant aspirin, clopidogrel, and warfarin therapy after percutaneous coronary intervention (PCI), and to identify patient characteristics that increase the risk of hemorrhage. DESIGN: Retrospective, matched cohort study. SETTING: Academic medical center and affiliated outpatient offices. PATIENTS: The active group consisted of 97 patients who underwent PCI from January 1, 2000-September 30, 2005, and received warfarin, aspirin, and clopidogrel; the control group consisted of 97 patients who were individually matched to patients in the active group by procedure type, procedure year, age, and sex. Control patients received aspirin and clopidogrel. MEASUREMENTS AND MAIN RESULTS: Clinical data were collected from inpatient records, outpatient physician office records, and telephone surveys administered to patients or caregivers. The primary end point was major bleeding. The median duration of follow-up after index procedure was 182 days (range 0-191 days) in the active group and 182 days (range 0-213 days) in the control group. Fifty-seven (59%) of the 97 patients in the active group received warfarin for atrial fibrillation. There were 14 major bleeds in the active group (including 1 death) and 3 major bleeds in the control group during the study period. Mean international normalized ratio at the time of bleeding was 3.4. Hazard ratio for major bleeding was 5.0 in patients receiving warfarin therapy (95% confidence interval 1.4-17.8, p=0.012). Aspirin dose, age, sex, body mass index, history of hypertension, diabetes mellitus, intraprocedural glycoprotein IIb-IIIa or anticoagulant type, and postprocedural anticoagulant use did not have a significant effect on the risk of major bleeding. CONCLUSION: Warfarin was an independent predictor of major bleeding after PCI in patients receiving dual antiplatelet therapy. Prospective data to further characterize the safety of concomitant warfarin and dual antiplatelet therapy after PCI are needed.