Myocardial interstitial fibrosis is part of the advanced disease stage of most cardiovascular pathologies. It has been characterized histologically in various disease settings from hypertensive heart ...disease and diabetic cardiomyopathy to severe aortic stenosis. It is also involved in the process of aging. In cardiovascular medicine, myocardial interstitial fibrosis is associated with several adverse outcomes, especially heart failure (HF) and sudden cardiac death. Until recently, clinical measures of interstitial fibrosis could only be made by invasive myocardial biopsy. The availability of cardiac magnetic resonance (CMR) T1 mapping techniques allows for the indirect measurement of interstitial space characteristics and extracellular volume size, which is closely correlated with collagen content and interstitial infiltration by amyloid and other molecules. There has been significant improvement in the accuracy and reproducibility of T1 acquisition sequences in the last decade; however, the correct use of this technique requires a solid CMR expertise in daily imaging practice. CMR has become the gold standard to assess left ventricular (LV) remodeling and functional features associated with interstitial fibrosis. These features can be detected in the early stages of HF. The main objective of this paper is to review the relevant results of preclinical and clinical observational studies that demonstrate the prognostic impact of interstitial fibrosis assessed by T1 mapping, as well as adverse left ventricular remodeling, as determinants of HF. Therefore, this review focuses on the pathological mechanisms underlying LV remodeling and interstitial fibrosis, in addition to the technical considerations involved in the assessment of interstitial LV fibrosis by CMR. It provides a thorough review of clinical evidence that demonstrates the association of interstitial fibrosis and other-CMR derived LV phenotypes with Stages A and B HF.
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•The myocardium undergoes important tissue composition (hypertrophy, interstitial and replacement fibrosis, and so on) and remodeling changes in Stage A and B HF.•CMR offers a comprehensive and reproducible assessment of LV tissue and anatomy modifications, with the potential to monitor different phenotypes in Stage A and B HF.•T1 mapping and ECV assessment by CMR requires careful acquisition protocol and solid expertise for routine practice.•Clinical use of these CMR measurements for therapeutic management still requires randomized controlled clinical trials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study assessed whether impaired fasting glucose (IFG), insulin resistance, and waist-to-hip ratio (WHR) had effects on cardiac remodeling, independent of obesity, in the MESA (Multi-Ethnic Study ...of Atherosclerosis) trial.
Recent studies have suggested that central obesity and insulin resistance may be primary mediators of obesity-related cardiac remodeling independent of body mass index (BMI).
We investigated 4,364 subjects without diabetes in the MESA trial. IFG (100 to 125 mg/dl) or insulin resistance (by homeostatic model assessment of insulin resistance HOMA-IR) and WHR were used for cardiometabolic phenotyping. Multivariate linear regression analysis was used to determine the effects of the cardiometabolic markers on left ventricular (LV) remodeling, assessed primarily through the LV mass-to-volume ratio obtained by cine cardiac magnetic resonance imaging.
Individuals with IFG were more likely to be older and hypertensive, with increased prevalence of cardiometabolic risk factors regardless of BMI. In each quartile of BMI, subjects with above-median HOMA-IR, above-median WHR, or IFG had a higher LV mass-to-volume ratio (p < 0.05 for all). HOMA-IR (p < 0.0001), WHR (p < 0.0001), and the presence of IFG (p = 0.04), but not BMI (p = 0.24), were independently associated with LV mass-to-volume ratio after adjustment for age, sex, hypertension, race, and dyslipidemia.
Insulin resistance and WHR were associated with concentric LV remodeling independent of BMI. These results support the emerging hypothesis that the cardiometabolic phenotype, defined by insulin resistance and central obesity, may play a critical role in LV remodeling independently of BMI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The extent of the peri-infarct zone by magnetic resonance imaging (MRI) has been related to all-cause mortality in patients with coronary artery disease. This relationship may result from ...arrhythmogenesis in the infarct border. However, the relationship between tissue heterogeneity in the infarct periphery and arrhythmic substrate has not been investigated. In the present study, we quantify myocardial infarct heterogeneity by contrast-enhanced MRI and relate it to an electrophysiological marker of arrhythmic substrate in patients with left ventricular (LV) systolic dysfunction undergoing prophylactic implantable cardioverter defibrillator placement.
Before implantable cardioverter defibrillator implantation for primary prevention of sudden cardiac death, 47 patients underwent cine and contrast-enhanced MRI to measure LV function, volumes, mass, and infarct size. A method for quantifying the heterogeneous infarct periphery and the denser infarct core is described. MRI indices were related to inducibility of sustained monomorphic ventricular tachycardia during electrophysiological or device testing. For the noninducible versus inducible patients, LV ejection fraction (30+/-10% versus 29+/-7%, P=0.79), LV end-diastolic volume (220+/-70 versus 228+/-57 mL, P=0.68), and infarct size by standard contrast-enhanced MRI definitions (P=NS) were similar. Quantification of tissue heterogeneity at the infarct periphery was strongly associated with inducibility for monomorphic ventricular tachycardia (noninducible versus inducible: 13+/-9 versus 19+/-8 g, P=0.015) and was the single significant factor in a stepwise logistic regression.
Tissue heterogeneity is present and quantifiable within human infarcts. More extensive tissue heterogeneity correlates with increased ventricular irritability by programmed electrical stimulation. These findings support the hypothesis that anatomic tissue heterogeneity increases susceptibility to ventricular arrhythmias in patients with prior myocardial infarction and LV dysfunction.
•Valve calcium progression and heart failure risk was assessed in a diverse cohort.•Progression of valve calcification was associated with increased heart failure risk.•Association seen for heart ...failure with preserved but not reduced ejection fraction.•This was independent of interim coronary heart disease & atrial fibrillation events.
Heart failure (HF) is a leading cause of morbidity. Strategies for preventing HF are paramount. Prevalent extracoronary calcification is associated with HF risk but less is known about progression of mitral annular (MAC) and aortic valve calcification (AVC) and HF risk. Progression of valvular calcification (VC) interval change of >0 units/yr was assessed by 2 cardiac computed tomography scans over a median of 2.4 years. We used Cox regression to determine the risk of adjudicated HF and linear mixed effects models to determine 10-year change in left ventricular (LV) parameters measured by cardiac magnetic resonance imaging associated with VC progression. We studied 5,591 MESA participants free of baseline cardiovascular disease. Mean ± SD age was 62 ± 10 years; 53% women; 83% had no VC progression, 15% progressed at 1 site (AVC or MAC) and 3% at both sites. There were 251 incident HF over 15 years. After adjusting for cardiovascular risk factors, the hazard ratios (95% confidence interval) of HF associated with VC progression at 1 and 2 sites were 1.62 (1.21 to 2.17) and 1.88 (1.14 to 3.09), respectively, compared with no progression (p-for-trend <0.001). Hazard ratios were higher for HFpEF (2.52 1.63 to 3.90 and 2.49 1.19 to 5.25) but nonsignificant for HFrEF. Both AVC (1.61 1.19 to 2.19) and MAC (1.50 1.09 to 2.07) progression were associated with HF. VC was associated with worsening of some LV parameters over 10 years. In conclusion, VC progression was associated with increased risk of HF and change in LV function. Interventions targeted at reducing VC progression may also impact HF risk, particularly HFpEF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Heart failure (HF) and atrial fibrillation (AF) are growing in prevalence worldwide. Few studies have assessed to what extent stage 1 hypertension in the 2017 American College of Cardiology/American ...Heart Association blood pressure (BP) guidelines is associated with incident HF and AF.
Analyses were conducted with a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018 (n=2 196 437; mean age, 44.0±10.9 years; 58.4% men). No participants were taking antihypertensive medication or had a known history of cardiovascular disease. Each participant was categorized as having normal BP (systolic BP <120 mm Hg and diastolic BP <80 mm Hg; n=1 155 885), elevated BP (systolic BP 120-129 mm Hg and diastolic BP <80 mm Hg; n=337 390), stage 1 hypertension (systolic BP 130-139 mm Hg or diastolic BP 80-89 mm Hg; n=459 820), or stage 2 hypertension (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg; n=243 342). Using Cox proportional hazards models, we identified associations between BP groups and HF/AF events. We also calculated the population attributable fractions to estimate the proportion of HF and AF events that would be preventable if participants with stage 1 and stage 2 hypertension were to have normal BP.
Over a mean follow-up of 1112±854 days, 28 056 incident HF and 7774 incident AF events occurred. After multivariable adjustment, hazard ratios for HF and AF events were 1.10 (95% CI, 1.05-1.15) and 1.07 (95% CI, 0.99-1.17), respectively, for elevated BP; 1.30 (95% CI, 1.26-1.35) and 1.21 (95% CI, 1.13-1.29), respectively, for stage 1 hypertension; and 2.05 (95% CI, 1.97-2.13) and 1.52 (95% CI, 1.41-1.64), respectively, for stage 2 hypertension versus normal BP. Population attributable fractions for HF associated with stage 1 and stage 2 hypertension were 23.2% (95% CI, 20.3%-26.0%) and 51.2% (95% CI, 49.2%-53.1%), respectively. The population attributable fractions for AF associated with stage 1 and stage 2 hypertension were 17.4% (95% CI, 11.5%-22.9%) and 34.3% (95% CI, 29.1%-39.2%), respectively.
Both stage 1 hypertension and stage 2 hypertension were associated with a greater incidence of HF and AF in the general population. The American College of Cardiology/American Heart Association BP classification system may help identify adults at higher risk for HF and AF events.
The purpose of this study was to assess the impact of patient population characteristics on accuracy by computed tomography angiography (CTA) to detect obstructive coronary artery disease (CAD).
The ...ability of CTA to exclude obstructive CAD in patients of different pre-test probabilities and in presence of coronary calcification remains uncertain.
For the CORE-64 (Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography) study, 371 patients underwent CTA and cardiac catheterization for the detection of obstructive CAD, defined as ≥50% luminal stenosis by quantitative coronary angiography (QCA). This analysis includes 80 initially excluded patients with a calcium score ≥600. Area under the receiver-operating characteristic curve (AUC) was used to evaluate CTA diagnostic accuracy compared to QCA in patients according to calcium score and pre-test probability of CAD.
Analysis of patient-based quantitative CTA accuracy revealed an AUC of 0.93 (95% confidence interval CI: 0.90 to 0.95). The AUC remained 0.93 (95% CI: 0.90 to 0.96) after excluding patients with known CAD but decreased to 0.81 (95% CI: 0.71 to 0.89) in patients with calcium score ≥600 (p = 0.077). While AUCs were similar (0.93, 0.92, and 0.93, respectively) for patients with intermediate, high pre-test probability for CAD, and known CAD, negative predictive values were different: 0.90, 0.83, and 0.50, respectively. Negative predictive values decreased from 0.93 to 0.75 for patients with calcium score <100 or ≥100, respectively (p = 0.053).
Both pre-test probability for CAD and coronary calcium scoring should be considered before using CTA for excluding obstructive CAD. For that purpose, CTA is less effective in patients with calcium score ≥600 and in patients with a high pre-test probability for obstructive CAD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The ability to distinguish dysfunctional but viable myocardium from nonviable tissue has important prognostic implications after myocardial infarction. The purpose of this study was to validate the ...accuracy of contrast-enhanced multidetector computed tomography (MDCT) for quantifying myocardial necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion myocardial infarction.
Ten dogs and 7 pigs underwent balloon occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm x 32 slice) was performed before occlusion and 90 minutes (canine) or 8 weeks (porcine) after reperfusion. MDCT images were analyzed to define infarct size/extent and microvascular obstruction and compared with postmortem myocardial staining (triphenyltetrazolium chloride) and microsphere blood flow measurements. Acute and chronic infarcts by MDCT were characterized by hyperenhancement, whereas regions of microvascular obstruction were characterized by hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium chloride staining (acute infarcts 21.1+/-7.2% versus 20.4+/-7.4%, mean difference 0.7%; chronic infarcts 4.15+/-1.93% versus 4.92+/-2.06%, mean difference -0.76%) and accurately reflected morphology and the transmural extent of injury in all animals. Peak hyperenhancement of infarcted regions occurred approximately 5 minutes after contrast injection. MDCT-derived regions of microvascular obstruction were also identified accurately in acute studies and correlated with reduced flow regions as measured by microsphere blood flow.
The spatial extent of acute and healed myocardial infarction can be determined and quantified accurately with contrast-enhanced MDCT. This feature, combined with existing high-resolution MDCT coronary angiography, may have important implications for the comprehensive assessment of cardiovascular disease.
Frequent premature ventricular contractions (PVCs) can induce cardiomyopathy (PVC CM). We sought to use cardiac magnetic resonance imaging (CMR) to quantify changes in cardiac structure and function ...of cardiomyopathy patients following catheter ablation for PVCs. Patients undergoing PVC ablation at the Johns Hopkins Hospital with pre-procedural CMR from 2010 to 2018 were included in this study. CMR Images were analyzed to collect information on cardiac structure and function as well as to quantify scar. Of the total 51 included patients, PVC CM (LVEF < 45%) was observed in 51% (n = 29). Of these, 19 had post-ablation ejection fractions quantified, with 78.9% (n = 15) recovering function. Global longitudinal strain was significantly correlated with LVEF (OR 1.831, p < 0.01) but did not predict recovery of function. RV origin of PVCs was more common in the preserved LVEF group but was also significantly correlated with persistently reduced EF post-ablation in the PVC CM group. Scar burden was not correlated with either cardiac function or post-ablation recovery of function. In this cohort, there were no significant CMR findings to predict subsequent recovery of EF after ablation among those with PVC CM. PVC origin in the RV was associated with persistently reduced LVEF after ablation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The goal of these studies was to determine the association between cardiovascular autonomic neuropathy (CAN) and indices of left ventricle (LV) structure and function in patients with type 1 diabetes ...(T1DM) in the DCCT/EDIC (Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications) study.
The pathophysiology of LV dysfunction in T1DM remains unclear, especially when the LV ejection fraction (EF) is preserved. Whether CAN is associated with LV dysfunction is unclear.
Indices of LV structure and function were obtained by cardiac magnetic resonance imaging (CMRI). CAN was assessed by cardiovascular reflex testing (R-R response to paced breathing, Valsalva ratio, and blood pressure response to standing). Analyses were performed in 966 DCCT/EDIC participants with valid CMRI and CAN data (mean age 51 years, 52% men, mean diabetes duration 29 years, and mean glycosylated hemoglobin 7.9%).
Systolic function (EF, end-systolic and end-diastolic volumes, stroke volumes) was not different in 371 subjects with CAN compared with 595 subjects without CAN. In multiple-adjusted analyses, participants with either abnormal R-R variation or a composite of abnormal R-R variation, abnormal Valsalva ratio, and postural blood pressure changes had significantly higher LV mass, mass-to-volume-ratio, and cardiac output compared with those with normal tests (p < 0.0001 for all). After further adjustment for traditional cardiovascular risk factors, subjects with abnormal R-R variation had higher LV mass and cardiac output compared with those with a normal R-R variation (p < 0.05).
In this large cohort of patients with T1DM, CAN is associated with increased LV mass and concentric remodeling as assessed by CMRI independent of age, sex, and other factors. (Diabetes Control and Complications Trial DCCT; NCT00360815) (Epidemiology of Diabetes Interventions and Complications EDIC; NCT00360893).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Better models to identify individuals at low risk of ventricular arrhythmia (VA) are needed for implantable cardioverter-defibrillator (ICD) candidates to mitigate the risk of ICD-related ...complications. We designed the CERTAINTY study (CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia) with deep learning for VA risk prediction from cine cardiac magnetic resonance (CMR). Using a training cohort of primary prevention ICD recipients (n = 350, 97 women, median age 59 years, 178 ischemic cardiomyopathy) who underwent CMR immediately prior to ICD implantation, we developed two neural networks: Cine Fingerprint Extractor and Risk Predictor. The former extracts cardiac structure and function features from cine CMR in a form of cine fingerprint in a fully unsupervised fashion, and the latter takes in the cine fingerprint and outputs disease outcomes as a cine risk score. Patients with VA (n = 96) had a significantly higher cine risk score than those without VA. Multivariate analysis showed that the cine risk score was significantly associated with VA after adjusting for clinical characteristics, cardiac structure and function including CMR-derived scar extent. These findings indicate that non-contrast, cine CMR inherently contains features to improve VA risk prediction in primary prevention ICD candidates. We solicit participation from multiple centers for external validation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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