Contemporary Data on the Status and Medical Management of Acute Heart Failure.

PURPOSE OF REVIEW: Acute heart failure (AHF) is among the leading causes for unplanned hospital admission. Despite advancements in the management of chronic heart failure, the prognosis of AHF remains poor with high in-hospital mortality and increased rates of unfavorable post-discharge outcomes. With this review, we aim to summarize current data on AHF epidemiology, focus on the different patient profiles and classifications, and discuss management, including novel therapeutic options in this area. RECENT FINDINGS: There is significant heterogeneity among patients admitted for AHF in their baseline characteristics, heart failure (HF) aetiology and precipitating factors leading to decompensation. A novel classification scheme based on four distinct clinical scenarios has been included in the most recent ESC guidelines, in an effort to better risk stratify patients and guide treatment. Intravenous diuretics, vasodilators, and inotropes remain the cornerstone of management in the acute phase, and expansion of use of mechanical circulatory support has been noted in recent years. Meanwhile, many treatments that have proved their value in chronic heart failure demonstrate promising results in the setting of AHF and research in this field is currently ongoing. Acute heart failure remains a major health challenge with high in-hospital mortality and unfavorable post-discharge outcomes. Admission for acute HF represents a window of opportunity for patients to initiate appropriate treatment as soon as possible after stabilization. Future studies are needed to elucidate which patients will benefit the most by available therapies and define the optimal timing for treatment implementation.

Evaluation of mitral regurgitation by cardiac magnetic resonance and transthoracic echocardiography: a systematic review and meta-analysis.

Transthoracic echocardiography (TTE) and Cardiac Magnetic Resonance (CMR) have complementary roles in the severity grading of mitral regurgitation (MR). Our objective was to systematically review the correlation of MR severity as assessed by TTE and CMR. We searched MEDLINE and Cochrane Library for original series published between January 1st, 2000 and March 23rd, 2020. We used Cohen's kappa coefficient to measure agreement between modalities. We plotted a hierarchical summary receiver operator characteristic (HSROC) curve and estimated the area under the curve (AUC) to assess the concordance between the two imaging modalities for the detection of severe MR. We identified 858 studies, of which 65 underwent full-text assessment and 8 were included in the meta-analysis. A total of 718 patients were included (425 males, 59%) in the final analysis. There was significant heterogeneity in the methods used and considerable variation in kappa coefficient, ranging from 0.10 to 0.48. Seven out of eight studies provided the necessary data to plot HSROC curves and calculate the AUC. The AUC for detecting severe MR was 0.83 (95% CI 0.80 to 0.86), whereas the AUC for detecting moderate to severe MR was 0.83 (95% CI 0.79 to 0.86). The agreement between TTE and CMR in MR severity evaluation is modest across the entire spectrum of severity grading. However, when focusing on patients with at least moderate MR the concordance between TTE and CMR is very good. Further prospective studies comparing hard clinical endpoints based on the CMR and TTE assessment of MR severity are needed.

Atrial Fibrillation Is Associated with Cognitive Impairment, All-Cause Dementia, Vascular Dementia, and Alzheimer's Disease: a Systematic Review and Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia in patients with stroke history. However, the association between AF and cognitive impairment in broader populations is less clear. OBJECTIVE: To systematically review and quantitatively synthesize the existing evidence regarding the association of AF with cognitive impairment of any severity and etiology and dementia. METHODS: Medline, Scopus, and Cochrane Central were searched in order to identify studies investigating the association between AF and cognitive impairment (or dementia) cross-sectionally and longitudinally. Studies encompassing and analyzing exclusively patients with stroke history were excluded. A random-effects model meta-analysis was conducted. Potential sources of between-study heterogeneity were investigated via subgroup and meta-regression analyses. Sensitivity analyses including only studies reporting data on stroke-free patients, vascular dementia, and Alzheimer's disease were performed. RESULTS: In total, 43 studies were included. In the pooled analysis, AF was significantly associated with dementia (adjusted OR, 1.6; 95% CI, 1.3 to 2.1; I2, 31%) and the combined endpoint of cognitive impairment or dementia (pooled adjusted OR, 1.5; 95% CI, 1.4 to 1.8; I2, 34%). The results were significant, even when studies including only stroke-free patients were pooled together (unadjusted OR, 2.2; 95% CI, 1.4 to 3.5; I2, 96%), but the heterogeneity rates were high. AF was significantly associated with increased risk of both vascular (adjusted OR, 1.7; 95% CI, 1.2 to 2.3; I2, 43%) and Alzheimer's dementia (adjusted HR, 1.4; 95% CI, 1.2 to 1.6; I2, 42%). CONCLUSION: AF increases the risk of cognitive impairment, all-cause dementia, vascular dementia, and Alzheimer's disease. Future studies should employ interventions that may delay or even prevent cognitive decline in AF patients.

Pregnancy associated plasma protein-A as a prognostic biomarker of all-cause mortality and cardiovascular events in patients presenting with chest pain: a systematic review.

AIM: Novel biomarkers have been proposed for identification of patients at greater risk of future adverse events among those presenting with chest pain. In this review, we aim to elucidate the ability of pregnancy associated plasma protein-A (PAPP-A) to predict mortality and other cardiovascular events in this patient population. METHODS: A literature search of the electronic databases Medline, Scopus, Cochrane Library and ClinicalTrials.gov was performed in order to identify studies investigating the utility of PAPP-A to predict mortality and adverse cardiovascular events in patients with chest pain. RESULTS: Eight studies met our inclusion criteria. Five of these studies pertained to patients with confirmed ischemic chest pain, while the rest included patients presenting with chest pain possibly due to acute coronary syndrome, irrespectively of the underlying cause. Although the results for long-term events were inconclusive in both groups of patients, higher PAPP-A concentrations were found to be a significant predictor of short-term adverse events in patients with confirmed ischemic chest pain. CONCLUSIONS: PAPP-A appears to be a potentially useful biomarker for short-term risk stratification of patients presenting with chest pain of ischemic origin. However, there is an eminent need for more standardized clinical studies investigating the prognostic value of this biomarker.

The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study.

BACKGROUND: Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity. METHODS: Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate. RESULTS: When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max. CONCLUSIONS: Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

Determination of Clinical Outcome in Mitral Regurgitation With Cardiovascular Magnetic Resonance Quantification.

BACKGROUND: Surgery for severe mitral regurgitation is indicated if symptoms or left ventricular dilation or dysfunction occur. However, prognosis is already reduced by this stage, and earlier surgery on asymptomatic patients has been advocated if valve repair is likely, but identifying suitable patients for early surgery is difficult. Quantifying the regurgitation may help, but evidence for its link with outcome is limited. Cardiovascular magnetic resonance (CMR) can accurately quantify mitral regurgitation, and we examined whether this was associated with the future need for surgery. METHODS AND RESULTS: One hundred nine asymptomatic patients with echocardiographic moderate or severe mitral regurgitation had baseline CMR scans and were followed up for up to 8 years (mean, 2.5±1.9 years). CMR quantification accurately identified patients who progressed to symptoms or other indications for surgery: 91% of subjects with regurgitant volume ≤55 mL survived to 5 years without surgery compared with only 21% with regurgitant volume >55 mL (P<0.0001). A similar separation was observed for regurgitant fraction ≤40% and >40%. CMR-derived end-diastolic volume index showed a weaker association with outcome (proportions surviving without surgery at 5 years, 90% for left ventricular end-diastolic volume index <100 mL/m(2) versus 48% for ≥100 mL/m(2)) and added little to the discriminatory power of regurgitant fraction/volume alone. CONCLUSIONS: CMR quantification of mitral regurgitation was associated with the development of symptoms or other indications for surgery and showed better discriminatory ability than the reference-standard CMR-derived ventricular volumes. CMR may be able to identify appropriate patients for early surgery, with the potential to change clinical practice, although the clinical benefits of early surgery require confirmation in a clinical trial.

Lone Atrial Fibrillation Is Associated With Impaired Left Ventricular Energetics That Persists Despite Successful Catheter Ablation.

BACKGROUND: Lone atrial fibrillation (AF) may reflect a subclinical cardiomyopathy that persists after sinus rhythm (SR) restoration, providing a substrate for AF recurrence. To test this hypothesis, we investigated the effect of restoring SR by catheter ablation on left ventricular (LV) function and energetics in patients with AF but no significant comorbidities. METHODS: Fifty-three patients with symptomatic paroxysmal or persistent AF and without significant valvular disease, uncontrolled hypertension, coronary artery disease, uncontrolled thyroid disease, systemic inflammatory disease, diabetes mellitus, or obstructive sleep apnea (ie, lone AF) undergoing ablation and 25 matched control subjects in SR were investigated. Magnetic resonance imaging quantified LV ejection fraction (LVEF), peak systolic circumferential strain (PSCS), and left atrial volumes and function, whereas phosphorus-31 magnetic resonance spectroscopy evaluated ventricular energetics (ratio of phosphocreatine to ATP). AF burden was determined before and after ablation by 7-day Holter monitoring; intermittent ECG event monitoring was also undertaken after ablation to investigate for asymptomatic AF recurrence. RESULTS: Before ablation, both LV function and energetics were significantly impaired in patients compared with control subjects (LVEF, 61% [interquartile range (IQR), 52%-65%] versus 71% [IQR, 69%-73%], P<0.001; PSCS, -15% [IQR, -11 to -18%] versus -18% [IQR, -17% to -19%], P=0.002; ratio of phosphocreatine to ATP, 1.81±0.35 versus 2.05±0.29, P=0.004). As expected, patients also had dilated and impaired left atria compared with control subjects (all P<0.001). Early after ablation (1-4 days), LVEF and PSCS improved in patients recovering SR from AF (LVEF, 7.0±10%, P=0.005; PSCS, -3.5±4.3%, P=0.001) but were unchanged in those in SR during both assessments (both P=NS). At 6 to 9 months after ablation, AF burden reduced significantly (from 54% [IQR, 1.5%-100%] to 0% [IQR 0%-0.1%]; P<0.001). However, LVEF and PSCS did not improve further (both P=NS) and remained impaired compared with control subjects (P<0.001 and P=0.003, respectively). Similarly, there was no significant improvement in atrial function from before ablation (P=NS), and this remained lower than in control subjects (P<0.001). The ratio of phosphocreatine to ATP was unaffected by heart rhythm during assessment and AF burden before ablation (both P=NS). It was unchanged after ablation (P=0.57), remaining lower than in control subjects regardless of both recovery of SR and freedom from recurrent AF (P=0.006 and P=0.002, respectively). CONCLUSIONS: Patients with lone AF have impaired myocardial energetics and subtle LV dysfunction, which do not normalize after ablation. These findings suggest that AF may be the consequence (rather than the cause) of an occult cardiomyopathy, which persists despite a significant reduction in AF burden after ablation.

Adenosine stress CMR T1-mapping detects early microvascular dysfunction in patients with type 2 diabetes mellitus without obstructive coronary artery disease.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction. METHODS: Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all patients by coronary computed tomographic angiography. RESULTS: All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients (from 1196 ± 32 ms to 1244 ± 44 ms, p < 0.001) and controls (from 1194 ± 26 ms to 1273 ± 44 ms, p < 0.001). T2DM patients showed blunted relative stress non-contrast T1 response (T2DM: ΔT1 = 4.1 ± 2.9% vs. CONTROLS: ΔT1 = 6.6 ± 2.6%, p = 0.007) due to a blunted maximal T1 during adenosine stress (T2DM 1244 ± 44 ms vs. controls 1273 ± 44 ms, p = 0.045). CONCLUSIONS: Patients with well controlled T2DM, even in the absence of arterial hypertension and significant CAD, exhibit blunted maximal non-contrast T1 response during adenosine vasodilatory stress, likely reflecting coronary microvascular dysfunction. Adenosine stress and rest T1 mapping can detect subclinical abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents. CMR may identify early features of the diabetic heart phenotype and subclinical cardiac risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention.

Correction to: Adenosine stress CMR T1-mapping detects early microvascular dysfunction in patients with type 2 diabetes mellitus without obstructive coronary artery disease.

In the original publication of this article [1] Fig. 1 was incorrect due to the use of a colour bar with wrong range in error.

Iatrogenic Lutembacher Syndrome after Percutaneous Mitral Commissurotomy.

Atrial septal defects (ASDs) are common immediately after percutaneous mitral commissurotomy (PMC). They are usually small, hemodynamically insignificant, and tend to decrease or disappear within 6 to 12 months. Herein, a case is described of persistent ASD in a patient with mitral valve stenosis who had undergone successful PMC three years previously. The patient had signs and symptoms of right heart failure and severe tricuspid regurgitation (TR) with borderline right ventricular systolic function on echocardiography, in addition to the ASD. Cardiac magnetic resonance (CMR) imaging played a significant role in decision-making by clarifying the anatomy of the ASD and severity of the shunt, measuring right ventricular systolic function, and providing absolute quantification for TR. The right ventricular systolic function was normal on CMR, rendering the patient suitable for surgical treatment. Persistent iatrogenic ASDs have become an increasingly common finding after invasive procedures requiring trans-septal puncture and the manipulation of catheters. Multimodality imaging can provide significant aid in the management of patients with valvular heart disease complicated by iatrogenic shunts.

Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus.

AIMS: Patients with type 2 diabetes mellitus (T2DM) are known to have impaired resting myocardial energetics and impaired myocardial perfusion reserve, even in the absence of obstructive epicardial coronary artery disease (CAD). Whether or not the pre-existing energetic deficit is exacerbated by exercise, and whether the impaired myocardial perfusion causes deoxygenation and further energetic derangement during exercise stress, is uncertain. METHODS AND RESULTS: Thirty-one T2DM patients, on oral antidiabetic therapies with a mean HBA1c of 7.4 ± 1.3%, and 17 matched controls underwent adenosine stress cardiovascular magnetic resonance for assessment of perfusion [myocardial perfusion reserve index (MPRI)] and oxygenation [blood-oxygen level-dependent (BOLD) signal intensity change (SIΔ)]. Cardiac phosphorus-MR spectroscopy was performed at rest and during leg exercise. Significant CAD (>50% coronary stenosis) was excluded in all patients by coronary computed tomographic angiography. Resting phosphocreatine to ATP (PCr/ATP) was reduced by 17% in patients (1.74 ± 0.26, P = 0.001), compared with controls (2.07 ± 0.35); during exercise, there was a further 12% reduction in PCr/ATP (P = 0.005) in T2DM patients, but no change in controls. Myocardial perfusion and oxygenation were decreased in T2DM (MPRI 1.61 ± 0.43 vs. 2.11 ± 0.68 in controls, P = 0.002; BOLD SIΔ 7.3 ± 7.8 vs. 17.1 ± 7.2% in controls, P < 0.001). Exercise PCr/ATP correlated with MPRI (r = 0.50, P = 0.001) and BOLD SIΔ (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SIΔ. CONCLUSION: The pre-existing energetic deficit in diabetic cardiomyopathy is exacerbated by exercise; stress PCr/ATP correlates with impaired perfusion and oxygenation. Our findings suggest that, in diabetes, coronary microvascular dysfunction exacerbates derangement of cardiac energetics under conditions of increased workload.

Exacerbation of cardiac energetic impairment during exercise in hypertrophic cardiomyopathy: a potential mechanism for diastolic dysfunction.

AIMS: Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden cardiac death in the young, with an excess of exercise-related deaths. The HCM sarcomere mutations increase the energy cost of contraction and impaired resting cardiac energetics has been documented by measurement of phosphocreatine/ATP (PCr/ATP) using (31)Phosphorus MR Spectroscopy ((31)P MRS). We hypothesized that cardiac energetics are further impaired acutely during exercise in HCM and that this would have important functional consequences. METHODS AND RESULTS: (31)P MRS was performed in 35 HCM patients and 20 age- and gender-matched normal volunteers at rest and during leg exercise with 2.5 kg ankle weights. Peak left-ventricular filling rates (PFRs) and myocardial perfusion reserve (MPRI) were calculated during adenosine stress. Resting PCr/ATP was significantly reduced in HCM (HCM: 1.71 ± 0.35, normal 2.14 ± 0.35 P < 0.0001). During exercise, there was a further reduction in PCr/ATP in HCM (1.56 ± 0.29, P = 0.02 compared with rest) but not in normals (2.16 ± 0.26, P = 0.98 compared with rest). There was no correlation between PCr/ATP reduction and cardiac mass, wall thickness, MPRI, or late-gadolinium enhancement. PFR and PCr/ATP were significantly correlated at rest (r = 0.48, P = 0.02) and stress (r = 0.53, P = 0.01). CONCLUSION: During exercise, the pre-existing energetic deficit in HCM is further exacerbated independent of hypertrophy, perfusion reserve, or degree of fibrosis. This is in keeping with the change at the myofilament level. We offer a potential explanation for exercise-related diastolic dysfunction in HCM.

Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease.

OBJECTIVE: To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease. APPROACH AND RESULTS: In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged. CONCLUSIONS: This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.

Adenosine stress native T1 mapping in severe aortic stenosis: evidence for a role of the intravascular compartment on myocardial T1 values.

BACKGROUND: Myocardial T1 relaxation times have been reported to be markedly abnormal in diverse myocardial pathologies, ascribed to interstitial changes, evaluated by T1 mapping and calculation of extracellular volume (ECV). T1 mapping is sensitive to myocardial water content of both intra- and extracellular in origin, but the effect of intravascular compartment changes on T1 has been largely neglected. We aimed to assess the role of intravascular compartment on native (pre-contrast) T1 values by studying the effect of adenosine-induced vasodilatation in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). METHODS: 42 subjects (26 patients with severe AS without obstructive coronary artery disease and 16 controls) underwent cardiovascular magnetic resonance at 3 T for native T1-mapping (ShMOLLI), first-pass perfusion (myocardial perfusion reserve index-MPRI) at rest and during adenosine stress, and late gadolinium enhancement (LGE). RESULTS: AS patients had increased resting myocardial T1 (1196±47 ms vs. 1168±27 ms, p=0.037), reduced MPRI (0.92±0.31 vs. 1.74±0.32, p<0.001), and increased left ventricular mass index (LVMI) and LGE volume compared to controls. During adenosine stress, T1 in AS was similar to controls (1240±51 ms vs. 1238±54 ms, p=0.88), possibly reflecting a similar level of maximal coronary vasodilatation in both groups. Conversely, the T1 response to stress was blunted in AS (ΔT1 3.7±2.7% vs. 6.0±4.2% in controls, p=0.013). Seven months after AVR (n=16) myocardial T1 and response to adenosine stress recovered towards normal. Native T1 values correlated with reduced MPRI, aortic valve area, and increased LVMI. CONCLUSIONS: Our study suggests that native myocardial T1 values are not only influenced by interstitial and intracellular water changes, but also by changes in the intravascular compartment. Performing T1 mapping during or soon after vasodilator stress may affect ECV measurements given that hyperemia alone appears to substantially alter T1 values.

Subclinical myocardial inflammation and diffuse fibrosis are common in systemic sclerosis--a clinical study using myocardial T1-mapping and extracellular volume quantification.

BACKGROUND: Systemic sclerosis (SSc) is characterised by multi-organ tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by T1 and extracellular volume (ECV) quantification, while focal myocardial inflammation and fibrosis may be detected by T2-weighted and late gadolinium enhancement (LGE), respectively, using cardiovascular magnetic resonance (CMR). We hypothesised that multiparametric CMR can detect subclinical myocardial involvement in patients with SSc. METHODS: 19 SSc patients (18 female, mean age 55 ± 10 years) and 20 controls (19 female, mean age 56 ± 8 years) without overt cardiovascular disease underwent CMR at 1.5T, including cine, tagging, T1-mapping, T2-weighted, LGE imaging and ECV quantification. RESULTS: Focal fibrosis on LGE was found in 10 SSc patients (53%) but none of controls. SSc patients also had areas of myocardial oedema on T2-weighted imaging (median 13 vs. 0% in controls). SSc patients had significantly higher native myocardial T1 values (1007 ± 29 vs. 958 ± 20 ms, p < 0.001), larger areas of myocardial involvement by native T1 >990 ms (median 52 vs. 3% in controls) and expansion of ECV (35.4 ± 4.8 vs. 27.6 ± 2.5%, p < 0.001), likely representing a combination of low-grade inflammation and diffuse myocardial fibrosis. Regardless of any regional fibrosis, native T1 and ECV were significantly elevated in SSc and correlated with disease activity and severity. Although biventricular size and global function were preserved, there was impairment in the peak systolic circumferential strain (-16.8 ± 1.6 vs. -18.6 ± 1.0, p < 0.001) and peak diastolic strain rate (83 ± 26 vs. 114 ± 16 s-1, p < 0.001) in SSc, which inversely correlated with diffuse myocardial fibrosis indices. CONCLUSIONS: Cardiac involvement is common in SSc even in the absence of cardiac symptoms, and includes chronic myocardial inflammation as well as focal and diffuse myocardial fibrosis. Myocardial abnormalities detected on CMR were associated with impaired strain parameters, as well as disease activity and severity in SSc patients. CMR may be useful in future in the study of treatments aimed at preventing or reducing adverse myocardial processes in SSc.

Native T1-mapping detects the location, extent and patterns of acute myocarditis without the need for gadolinium contrast agents.

BACKGROUND: Acute myocarditis can be diagnosed on cardiovascular magnetic resonance (CMR) using multiple techniques, including late gadolinium enhancement (LGE) imaging, which requires contrast administration. Native T1-mapping is significantly more sensitive than LGE and conventional T2-weighted (T2W) imaging in detecting myocarditis. The aims of this study were to demonstrate how to display the non-ischemic patterns of injury and to quantify myocardial involvement in acute myocarditis without the need for contrast agents, using topographic T1-maps and incremental T1 thresholds. METHODS: We studied 60 patients with suspected acute myocarditis (median 3 days from presentation) and 50 controls using CMR (1.5 T), including: (1) dark-blood T2W imaging; >(2) native T1-mapping (ShMOLLI); (3) LGE. Analysis included: (1) global myocardial T2 signal intensity (SI) ratio compared to skeletal muscle; (2) myocardial T1 times; (3) areas of injury by T2W, T1-mapping and LGE. RESULTS: Compared to controls, patients had more edema (global myocardial T2 SI ratio 1.71 ± 0.27 vs.1.56 ± 0.15), higher mean myocardial T1 (1011 ± 64 ms vs. 946 ± 23 ms) and more areas of injury as detected by T2W (median 5% vs. 0%), T1 (median 32% vs. 0.7%) and LGE (median 11% vs. 0%); all p < 0.001. A threshold of T1 > 990 ms (sensitivity 90%, specificity 88%) detected significantly larger areas of involvement than T2W and LGE imaging in patients, and additional areas of injury when T2W and LGE were negative. T1-mapping significantly improved the diagnostic confidence in an additional 30% of cases when at least one of the conventional methods (T2W, LGE) failed to identify any areas of abnormality. Using incremental thresholds, T1-mapping can display the non-ischemic patterns of injury typical of myocarditis. CONCLUSION: Native T1-mapping can display the typical non-ischemic patterns in acute myocarditis, similar to LGE imaging but without the need for contrast agents. In addition, T1-mapping offers significant incremental diagnostic value, detecting additional areas of myocardial involvement beyond T2W and LGE imaging and identified extra cases when these conventional methods failed to identify abnormalities. In the future, it may be possible to perform gadolinium-free CMR using cine and T1-mapping for tissue characterization and may be particularly useful for patients in whom gadolinium contrast is contraindicated.

Myocardial perfusion and oxygenation are impaired during stress in severe aortic stenosis and correlate with impaired energetics and subclinical left ventricular dysfunction.

BACKGROUND: Left ventricular (LV) hypertrophy in aortic stenosis (AS) is characterized by reduced myocardial perfusion reserve due to coronary microvascular dysfunction. However, whether this hypoperfusion leads to tissue deoxygenation is unknown. We aimed to assess myocardial oxygenation in severe AS without obstructive coronary artery disease, and to investigate its association with myocardial energetics and function. METHODS: Twenty-eight patients with isolated severe AS and 15 controls underwent cardiovascular magnetic resonance (CMR) for assessment of perfusion (myocardial perfusion reserve index-MPRI) and oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change) during adenosine stress. LV circumferential strain and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were assessed using tagging CMR and 31P MR spectroscopy, respectively. RESULTS: AS patients had reduced MPRI (1.1 ± 0.3 vs. controls 1.7 ± 0.3, p < 0.001) and BOLD SI change during stress (5.1 ± 8.9% vs. controls 18.2 ± 10.1%, p = 0.001), as well as reduced PCr/ATP (1.45 ± 0.21 vs. 2.00 ± 0.25, p < 0.001) and LV strain (-16.4 ± 2.7% vs. controls -21.3 ± 1.9%, p < 0.001). Both perfusion reserve and oxygenation showed positive correlations with energetics and LV strain. Furthermore, impaired energetics correlated with reduced strain. Eight months post aortic valve replacement (AVR) (n = 14), perfusion (MPRI 1.6 ± 0.5), oxygenation (BOLD SI change 15.6 ± 7.0%), energetics (PCr/ATP 1.86 ± 0.48) and circumferential strain (-19.4 ± 2.5%) improved significantly. CONCLUSIONS: Severe AS is characterized by impaired perfusion reserve and oxygenation which are related to the degree of derangement in energetics and associated LV dysfunction. These changes are reversible on relief of pressure overload and hypertrophy regression. Strategies aimed at improving oxygen demand-supply balance to preserve myocardial energetics and LV function are promising future therapies.

Determinants of functional mitral regurgitation severity in patients with ischemic cardiomyopathy versus nonischemic dilated cardiomyopathy.

AIMS: Functional mitral regurgitation (MR) is prevalent among patients with left ventricular (LV) dysfunction and is associated with a poorer prognosis. Our aim was to assess the primary determinants of MR severity in patients with ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Patients with functional MR secondary to ICM (n = 55) and DCM (n = 48) were prospectively enrolled. Effective regurgitant orifice (ERO) area, global LV remodeling, regional wall-motion abnormalities, and mitral apparatus deformity indices were assessed utilizing conventional and tissue Doppler echocardiography. ICM patients had more severe MR compared with DCM patients despite similar ejection fraction and functional status (ERO = 0.16 ± 0.08 cm(2) vs. ERO = 0.12 ± 0.70 cm(2) , respectively, P = 0.002). Regional myocardial systolic velocities in mid-inferior and mid-lateral wall were negatively correlated with ERO in ICM and DCM patients, respectively. Multivariate analysis identified coaptation height as the only independent determinant of ERO in both groups. In a subset of ICM patients (n = 9) with relatively high ERO despite low coaptation height, a higher prevalence of left bundle branch block was detected (88.9% vs. 46.7%, P = 0.02). CONCLUSIONS: Functional MR severity was chiefly determined by the extent of mitral apparatus deformity, and coaptation height can provide a rapid estimation of MR severity in heart failure patients. Additional contributory mechanisms in ICM patients include depressed myocardial systolic velocities in posteromedial papillary muscle attaching site and evidence of global LV dyssynchrony.