What to consider when implementing a tool for timely recognition of palliative care needs in heart failure: a context-based qualitative study.

BACKGROUND: Needs assessment tools can facilitate healthcare professionals in timely recognition of palliative care needs. Despite the increased attention for implementation of such tools, most studies provide little or no attention to the context of implementation. The aim of this study was to explore factors that contribute positively and negatively to timely screening of palliative care needs in advanced chronic heart failure. METHODS: Qualitative study using individual interviews and focus groups with healthcare professionals. The data were analysed using a deductive approach. The Consolidated Framework for Implementation Research was used to conceptualise the contextual factors. RESULTS: Twenty nine healthcare professionals with different backgrounds and working in heart failure care in the Southern and Eastern parts of the Netherlands participated. Several factors were perceived to play a role, such as perception and knowledge about palliative care, awareness of palliative care needs in advanced chronic heart failure, perceived difficulty when and how to start palliative care, limited acceptance to treatment boundaries in cardiology, limited communication and collaboration between healthcare professionals, and need for education and increased attention for palliative care in advanced chronic heart failure guidelines. CONCLUSIONS: This study clarified critical factors targeting patients, healthcare professionals, organisations to implement a needs assessment tool for timely recognition of palliative care needs in the context of advanced chronic heart failure. A multifaceted implementation strategy is needed which has attention for education, patient empowerment, interdisciplinary collaboration, identification of local champions, chronic heart failure specific guidelines and culture.

Cardiac MRI to Visualize Myocardial Damage after ST-Segment Elevation Myocardial Infarction: A Review of Its Histologic Validation.

Cardiac MRI is a noninvasive diagnostic tool using nonionizing radiation that is widely used in patients with ST-segment elevation myocardial infarction (STEMI). Cardiac MRI depicts different prognosticating components of myocardial damage such as edema, intramyocardial hemorrhage (IMH), microvascular obstruction (MVO), and fibrosis. But how do cardiac MRI findings correlate to histologic findings? Shortly after STEMI, T2-weighted imaging and T2* mapping cardiac MRI depict, respectively, edema and IMH. The acute infarct size can be determined with late gadolinium enhancement (LGE) cardiac MRI. T2-weighted MRI should not be used for area-at-risk delineation because T2 values change dynamically over the first few days after STEMI and the severity of T2 abnormalities can be modulated with treatment. Furthermore, LGE cardiac MRI is the most accurate method to visualize MVO, which is characterized by hemorrhage, microvascular injury, and necrosis in histologic samples. In the chronic setting post-STEMI, LGE cardiac MRI is best used to detect replacement fibrosis (ie, final infarct size after injury healing). Finally, native T1 mapping has recently emerged as a contrast material-free method to measure infarct size that, however, remains inferior to LGE cardiac MRI. Especially LGE cardiac MRI-defined infarct size and the presence and extent of MVO may be used to monitor the effect of new therapeutic interventions in the treatment of reperfusion injury and infarct size reduction. © RSNA, 2021 Online supplemental material is available for this article.

Cardiovascular magnetic resonance accurately detects obstructive coronary artery disease in suspected non-ST elevation myocardial infarction: a sub-analysis of the CARMENTA Trial.

BACKGROUND: Invasive coronary angiography (ICA) is still the reference test in suspected non-ST elevation myocardial infarction (NSTEMI), although a substantial number of patients do not have obstructive coronary artery disease (CAD). Early cardiovascular magnetic resonance (CMR) may be a useful gatekeeper for ICA in this setting. The main objective was to investigate the accuracy of CMR to detect obstructive CAD in NSTEMI. METHODS: This study is a sub-analysis of a randomized controlled trial investigating whether a non-invasive imaging-first strategy safely reduced the number of ICA compared to routine clinical care in suspected NSTEMI (acute chest pain, non-diagnostic electrocardiogram, high sensitivity troponin T > 14 ng/L), and included 51 patients who underwent CMR prior to ICA. A stepwise approach was used to assess the diagnostic accuracy of CMR to detect (1) obstructive CAD (diameter stenosis ≥ 70% by ICA) and (2) an adjudicated final diagnosis of acute coronary syndrome (ACS). First, in all patients the combination of cine, T2-weighted and late gadolinium enhancement (LGE) imaging was evaluated for the presence of abnormalities consistent with a coronary etiology in any sequence. Hereafter and only when the scan was normal or equivocal, adenosine stress-perfusion CMR was added. RESULTS: Of 51 patients included (63 ± 10 years, 51% male), 34 (67%) had obstructive CAD by ICA. The sensitivity, specificity and overall accuracy of the first step to diagnose obstructive CAD were 79%, 71% and 77%, respectively. Additional vasodilator stress-perfusion CMR was performed in 19 patients and combined with step one resulted in an overall sensitivity of 97%, specificity of 65% and accuracy of 86%. Of the remaining 17 patients with non-obstructive CAD, 4 (24%) had evidence for a myocardial infarction on LGE, explaining the modest specificity. The sensitivity, specificity and overall accuracy to diagnose ACS (n = 43) were 88%, 88% and 88%, respectively. CONCLUSION: CMR accurately detects obstructive CAD and ACS in suspected NSTEMI. Non-obstructive CAD is common with CMR still identifying an infarction in almost one-quarter of patients. CMR should be considered as an early diagnostic approach in suspected NSTEMI. TRIAL REGISTRATION: The CARMENTA trial has been registered at ClinicalTrials.gov with identifier NCT01559467.

Both beat-to-beat changes in RR-interval and left ventricular filling time determine ventricular function during atrial fibrillation.

AIMS: The irregular atrial electrical activity during atrial fibrillation (AF) is associated with a variable left ventricular (LV) systolic function. The mechanisms determining LV function during AF remain incompletely understood. We aimed at elucidating how changes in RR-interval and LV preload affect LV function during AF. METHODS AND RESULTS: Beat-to-beat speckle-tracking echocardiography was performed in 10 persistent AF patients. We evaluated the relation between longitudinal LV peak strain and preceding RR-interval during AF. We used the CircAdapt computational model to evaluate beat-to-beat preload and peak strain during AF for each patient by imposing the patient-specific RR-interval sequences and a non-contractile atrial myocardium. Generic simulations with artificial RR-interval sequences quantified the haemodynamic changes induced by sudden irregular beats. Clinical data and simulations both showed a larger sensitivity of peak strain to changes in preceding RR-interval at slow heart rate (HR) (cycle length, CL <750 ms) than at faster HR. Simulations explained this by a difference in preload of the current beat. Generic simulations confirmed a larger sensitivity of peak strain to preceding RR-interval at fast HR (CL = 600 ms: Δ peak strain = 3.7% vs. 900 ms: Δ peak strain = 0.3%) as in the patients. They suggested that longer LV activation with respect to preceding RR-interval is determinant for this sensitivity. CONCLUSIONS: During AF, longitudinal LV peak strain is highly variable, particularly at fast HR. Beat-to-beat changes in preload explain the differences in LV systolic function. Simulations revealed that a reduced diastolic LV filling time can explain the increased variability at fast HR.

Clinical assessment of aortic valve stenosis: Comparison between 4D flow MRI and transthoracic echocardiography.

BACKGROUND: The prevalence of valvular aortic stenosis (AS) increases as the population ages. Echocardiographic measurements of peak jet velocity (Vpeak ), mean pressure gradient (Pmean ), and aortic valve area (AVA) determine AS severity and play a pivotal role in the stratification towards valvular replacement. A multimodality imaging approach might be needed in cases of uncertainty about the actual severity of the stenosis. PURPOSE: To compare four-dimensional phase-contrast magnetic resonance (4D PC-MR), two-dimensional (2D) PC-MR, and transthoracic echocardiography (TTE) for quantification of AS. STUDY TYPE: Prospective. POPULATION: Twenty patients with various degrees of AS (69.3 ± 5.0 years). FIELD STRENGTH/SEQUENCES: 4D PC-MR and 2D PC-MR at 3T. ASSESSMENT: We compared Vpeak , Pmean , and AVA between TTE, 4D PC-MR, and 2D PC-MR. Flow eccentricity was quantified by means of normalized flow displacement, and its influence on the accuracy of TTE measurements was investigated. STATISTICAL TESTS: Pearson's correlation, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. RESULTS: 4D PC-MR measured higher Vpeak (r = 0.95, mean difference + 16.4 ± 10.7%, P <0.001), and Pmean (r = 0.92, mean difference + 14.9 ± 16.0%, P = 0.013), but a less critical AVA (r = 0.80, mean difference + 19.9 ± 20.6%, P = 0.002) than TTE. In contrast, unidirectional 2D PC-MR substantially underestimated AS severity when compared with TTE. Differences in Vpeak between 4D PC-MR and TTE showed to be strongly correlated with the eccentricity of the flow jet (r = 0.89, P <0.001). Use of 4D PC-MR improved the concordance between Vpeak and AVA (from 0.68 to 0.87), and between PGmean and AVA (from 0.68 to 0.86). DATA CONCLUSION: 4D PC-MR improves the concordance between the different AS parameters and could serve as an additional imaging technique next to TTE. Future studies should address the potential value of 4D PC-MR in patients with discordant echocardiographic parameters. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:472-480.

Integration of cardiac magnetic resonance imaging, electrocardiographic imaging, and coronary venous computed tomography angiography for guidance of left ventricular lead positioning.

AIMS: An appropriate left ventricular (LV) lead position is a pre-requisite for response to cardiac resynchronization therapy (CRT) and is highly patient-specific. The purpose of this study was to develop a non-invasive pre-procedural CRT-roadmap to guide LV lead placement to a coronary vein in late-activated myocardium remote from scar. METHODS AND RESULTS: Sixteen CRT candidates were prospectively included. Electrocardiographic imaging (ECGI), computed tomography angiography (CTA), and delayed enhancement cardiac magnetic resonance imaging (DE-CMR) were integrated into a 3D cardiac model (CRT-roadmap) using anatomic landmarks from CTA and DE-CMR. Electrocardiographic imaging was performed using 184 electrodes and a CT-based heart-torso geometry. Coronary venous anatomy was visualized using a designated CTA protocol. Focal scar was assessed from DE-CMR. Cardiac resynchronization therapy-roadmaps were constructed for all 16 patients [left bundle branch block: n = 6; intraventricular conduction disturbance: n = 8; narrow-QRS (ablate and pace strategy); n = 1; right bundle branch block: n = 1]. The number of coronary veins ranged between 3 and 4 per patient. The CRT-roadmaps showed no (n = 5), 1 (n = 6), or 2 (n = 5) veins per patient located outside scar in late-activated myocardium [≥50% QRS duration (QRSd)]. Final LV lead position was outside scar in late-activated myocardium in 11 out of 14 implanted patients, while a LV lead in scar was unavoidable in the remaining three patients. CONCLUSION: A non-invasive pre-implantation CRT-roadmap was feasible to develop in a case series by integration of coronary venous anatomy, myocardial-scar localization, and epicardial electrical activation patterns, anticipating on clinically relevant features.

The electrocardiogram as a predictor of successful pharmacological cardioversion and progression of atrial fibrillation.

Aims: Non-invasive characterization of atrial fibrillation (AF) substrate complexity based on the electrocardiogram (ECG) may improve outcome prediction in patients receiving rhythm control therapies for AF. Multiple parameters to assess AF complexity and predict treatment outcome have been suggested. A comparative study of the predictive performance of complexity parameters on response to therapy and progression of AF in a large patient population is needed to standardize non-invasive analysis of AF. Methods and results: A large variety of ECG complexity parameters were systematically compared in patients with recent onset AF undergoing pharmacological cardioversion (PCV) with flecainide. Parameters were computed on 10-s 12-lead ECGs of 221 patients before drug administration. The ability of ECG parameters to predict successful PCV and progression to persistent AF (mean follow-up 49 months) was evaluated and compared with common clinical predictors. Optimal prediction performance of successful PCV using only one ECG parameter was low, using dominant atrial frequency [lead II, receiver operating area under curve (AUC) 0.66, 95% confidence interval [0.64-0.67]], but the optimal combination of several ECG parameters strongly improved predictive performance (AUC 0.78 [0.76-0.79]). While predictive value of the optimal combination of clinical predictors was low (AUC 0.68 [0.66-0.70], using right atrial volume and weight), adding ECG parameters strongly increased performance (AUC 0.81 [0.79-0.82], P < 0.001). Interestingly, higher dominant frequency and higher f-wave amplitude were associated with increased risk of progression to persistent AF during follow-up. Conclusion: Assessment of AF complexity from 12-lead ECGs significantly improves prediction of successful PCV and progression to persistent AF compared with common clinical and echocardiographic predictors.

Acute chest pain in the high-sensitivity cardiac troponin era: A changing role for noninvasive imaging?

Management of patients with acute chest pain remains challenging. Cardiac biomarker testing reduces the likelihood of erroneously discharging patients with acute myocardial infarction (AMI). Despite normal contemporary troponins, physicians have still been reluctant to discharge patients without additional testing. Nowadays, the extremely high negative predictive value of current high-sensitivity cardiac troponin (hs-cTn) assays challenges this need. However, the decreased specificity of hs-cTn assays to diagnose AMI poses a new problem as noncoronary diseases (eg, pulmonary embolism, myocarditis, cardiomyopathies, hypertension, renal failure, etc) may also cause elevated hs-cTn levels. Subjecting patients with noncoronary diseases to unnecessary pharmacological therapy or invasive procedures must be prevented. Attempts to improve the positive predictive value to diagnose AMI by defining higher initial cutoff values or dynamic changes over time inherently lower the sensitivity of troponin assays. In this review, we anticipate a potential changing role of noninvasive imaging from ruling out myocardial disease when troponin values are normal toward characterizing myocardial disease when hs-cTn values are (mildly) abnormal.

MRS: a noninvasive window into cardiac metabolism.

A well-functioning heart requires a constant supply of a balanced mixture of nutrients to be used for the production of adequate amounts of adenosine triphosphate, which is the main energy source for most cellular functions. Defects in cardiac energy metabolism are linked to several myocardial disorders. MRS can be used to study in vivo changes in cardiac metabolism noninvasively. MR techniques allow repeated measurements, so that disease progression and the response to treatment or to a lifestyle intervention can be monitored. It has also been shown that MRS can predict clinical heart failure and death. This article focuses on in vivo MRS to assess cardiac metabolism in humans and experimental animals, as experimental animals are often used to investigate the mechanisms underlying the development of metabolic diseases. Various MR techniques, such as cardiac (31) P-MRS, (1) H-MRS, hyperpolarized (13) C-MRS and Dixon MRI, are described. A short overview of current and emerging applications is given. Cardiac MRS is a promising technique for the investigation of the relationship between cardiac metabolism and cardiac disease. However, further optimization of scan time and signal-to-noise ratio is required before broad clinical application. In this respect, the ongoing development of advanced shimming algorithms, radiofrequency pulses, pulse sequences, (multichannel) detection coils, the use of hyperpolarized nuclei and scanning at higher magnetic field strengths offer future perspective for clinical applications of MRS.

An FBN1 deep intronic mutation in a familial case of Marfan syndrome: an explanation for genetically unsolved cases?

Marfan syndrome (MFS) is caused by mutations in the FBN1 (fibrillin-1) gene, but approximately 10% of MFS cases remain genetically unsolved. Here, we report a new FBN1 mutation in an MFS family that had remained negative after extensive molecular genomic DNA FBN1 testing, including denaturing high-performance liquid chromatography, Sanger sequencing, and multiplex ligation-dependent probe amplification. Linkage analysis in the family and cDNA sequencing of the proband revealed a deep intronic point mutation in intron 56 generating a new splice donor site. This mutation results in the integration of a 90-bp pseudo-exon between exons 56 and 57 containing a stop codon, causing nonsense-mediated mRNA decay. Although more than 90% of FBN1 mutations can be identified with regular molecular testing at the genomic level, deep intronic mutations will be missed and require cDNA sequencing or whole-genome sequencing.

The role of cardiovascular magnetic resonance imaging and computed tomography angiography in suspected non-ST-elevation myocardial infarction patients: design and rationale of the CARdiovascular Magnetic rEsoNance imaging and computed Tomography Angiography (CARMENTA) trial.

BACKGROUND: Although high-sensitivity cardiac troponin (hs-cTn) substantially improves the early detection of myocardial injury, it lacks specificity for acute myocardial infarction (MI). In suspected non-ST-elevation MI, invasive coronary angiography (ICA) remains necessary to distinguish between acute MI and noncoronary myocardial disease (eg, myocarditis), unnecessarily subjecting the latter to ICA and associated complications. This trial investigates whether implementing cardiovascular magnetic resonance (CMR) or computed tomography angiography (CTA) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease, thereby preventing unnecessary ICA. STUDY DESIGN: In this prospective, single-center, randomized controlled clinical trial, 321 consecutive patients with acute chest pain, elevated hs-cTnT, and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies: (1) CMR, or (2) CTA early in the diagnostic process, or (3) routine clinical management. In the 2 investigational arms of the study, results of CMR or CTA will guide further clinical management. It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management, and unnecessary ICA will be prevented. The primary end point is the total number of patients undergoing ICA during initial admission. Secondary end points are 30-day and 1-year clinical outcome (major adverse cardiac events and major procedure-related complications), time to final diagnosis, quality of life, and cost-effectiveness. CONCLUSION: The CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non-ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management, with no detrimental effect on clinical outcome.

Incremental value of cardiovascular magnetic resonance over echocardiography in the detection of acute and chronic myocardial infarction.

BACKGROUND: Although echocardiography is used as a first line imaging modality, its accuracy to detect acute and chronic myocardial infarction (MI) in relation to infarct characteristics as assessed with late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is not well described. METHODS: One-hundred-forty-one echocardiograms performed in 88 first acute ST-elevation MI (STEMI) patients, 2 (IQR1-4) days (n = 61) and 102 (IQR92-112) days post-MI (n = 80), were pooled with echocardiograms of 36 healthy controls. 61 acute and 80 chronic echocardiograms were available for analysis (53 patients had both acute and chronic echocardiograms). Two experienced echocardiographers, blinded to clinical and CMR data, randomly evaluated all 177 echocardiograms for segmental wall motion abnormalities (SWMA). This was compared with LGE-CMR determined infarct characteristics, performed 104 ± 11 days post-MI. Enhancement on LGE-CMR matched the infarct-related artery territory in all patients (LAD 31%, LCx 12% and RCA 57%). RESULTS: The sensitivity of echocardiography to detect acute MI was 78.7% and 61.3% for chronic MI; specificity was 80.6%. Undetected MI were smaller, less transmural, and less extensive (6% [IQR3-12] vs. 15% [IQR9-24], 50 ± 14% vs. 61 ± 15%, 7 ± 3 vs. 9 ± 3 segments, p < 0.001 for all) and associated with higher left ventricular ejection fraction (LVEF) and non-anterior location as compared to detected MI (58 ± 5% vs. 46 ± 7%, p < 0.001 and 82% vs. 63%, p = 0.03). After multivariate analysis, LVEF and infarct size were the strongest independent predictors of detecting chronic MI (OR 0.78 [95%CI 0.68-0.88], p < 0.001 and OR 1.22 [95%CI0.99-1.51], p = 0.06, respectively). Increasing infarct transmurality was associated with increasing SWMA (p < 0.001). CONCLUSIONS: In patients presenting with STEMI, and thus a high likelihood of SWMA, the sensitivity of echocardiography to detect SWMA was higher in the acute than the chronic phase. Undetected MI were smaller, less extensive and less transmural, and associated with non-anterior localization and higher LVEF. Further work is needed to assess the diagnostic accuracy in patients with non-STEMI.

The predictive value of an ECG-estimated Acute Ischemia Index for prognosis of myocardial salvage and infarct healing 3months following inferior ST-elevated myocardial infarction.

BACKGROUND AND PURPOSE: Identification of prognostic markers can be used to stratify patients in the acute phase of ST-elevated myocardial infarction (STEMI) according to their potential to retain viable myocardium after reperfusion. The percentage of the myocardial area at risk (MaR) that is ischemic at admission, defined as the Acute Ischemia Index, is potentially salvageable. The percentage of the MaR viable at 3months post-reperfusion, by salvage and healing, was defined as the Chronic Salvage Index. A positive relationship between the Acute Ischemia Index and the Chronic Salvage Index was hypothesized. METHODS: Both indices were assessed by using the ECG indices Aldrich ST and Selvester QRS scores estimating the ischemic and infarcted myocardium. The study population comprised inferior STEMI patients. (N=59). RESULTS: A correlation of 0.253 (P=0.053) was found. CONCLUSIONS: These results are relevant and suggest evidence of a trend in the association between these indices.

A case report of a myocardial ischaemic attack: a novel hyperenhancement pattern on cardiac magnetic resonance in focal ischaemic injury.

Background: Delayed enhancement cardiac magnetic resonance (DE-CMR) is the reference standard for the non-invasive assessment of myocardial fibrosis. DE-CMR is able to distinguish ischaemic from non-ischaemic aetiologies based on differences in hyperenhancement distribution patterns. Hyperenhancement caused by ischaemic injury typically involves the endocardium, while hyperenhancement confined to the mid- and epicardial layers of the myocardium suggests a non-ischaemic aetiology. Case summary: This is a case of a 20-year-old male with an unremarkable medical history with an acute ST-elevation myocardial infarction. DE-CMR revealed two distinct patterns of hyperenhancement: (i) a 'normal' wavefront-ischaemic pattern, and (ii) multiple atypical mid-wall and epicardial areas of focal hyperenhancement. Invasive coronary angiography (ICA) and coronary computed tomographic angiography (CCTA) showed multiple intracoronary thrombi and distal emboli in the left anterior descending, ramus circumflexus, and in smaller branches of the LCA. All hyperenhancement patterns observed on DE-CMR perfectly matched the distribution territories of the affected coronary arteries. Discussion: This case with an acute myocardial infarction showed intracoronary thrombi and emboli on ICA and CCTA. Interestingly, DE-CMR showed two different patterns of hyperenhancement in the same territories of the coronary thrombi. This observation may challenge the concept that these non-endocardial areas of hyperenhancement on DE-CMR are always of non-ischaemic aetiology. It is hypothesized that occlusion of smaller distal branches of the coronary arteries may result in mid-wall or epicardial fibrosis as opposed to subendocardial fibrosis commonly found in patients with a large epicardial coronary occlusion. Clinicians should be aware of these atypical patterns to be able to initiate adequate medical therapy.

Evaluating subclinical left ventricular and left atrial dysfunction in idiopathic atrial fibrillation: A speckle-tracking based strain-analysis.

OBJECTIVE: A subset of patients with atrial fibrillation (AF) presents without established AF risk factors and normal left ventricular (LV) systolic function, called idiopathic AF (IAF). Traditionally, echocardiography derived LV dimensions and ejection fraction (EF) are used to exclude LV dysfunction in IAF, but their sensitivity is limited. Our objective is to evaluate the presence of subtle alterations in LV function despite normal LVEF in patients with IAF compared to healthy controls, using speckle-tracking echocardiography (STE) based global longitudinal strain (GLS). METHODS: Standard transthoracic echocardiography was performed in 80 patients with IAF and 129 healthy controls. Patients with overt cardiac disease as well as known established AF risk factors were excluded. STE analysis was performed to assess GLS of the LV, and left atrial strain (LAS). RESULTS: LVEF was normal and comparable between patients with IAF and healthy controls (63 ± 4% for both groups; p = 0.801). Mean GLS was within normal limits for both groups but statistically significantly more negative in patients with IAF (-20.6 ± 2.5% vs. -19.7 ± 2.5%; p = 0.016), however not when indexed for ventricular cycle length (p = 0.784). No differences in LA volume or non-indexed LAS were seen in patients with IAF compared to healthy controls. CONCLUSIONS: In this selected group of IAF patients, STE did not detect any overt LV or LA dysfunction compared to healthy controls. Thus, IAF occurred in these patients not only in the absence of established AF risk factors but also without evidence of ventricular or atrial dysfunction.

Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study.

BACKGROUND: Myotonic dystrophy type 1 (MD1) is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1. METHODS: Eighty MD1 patients underwent physical examination, electrocardiography (ECG), echocardiography and cardiovascular magnetic resonance (CMR). Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length. RESULTS: Functional and structural abnormalities were detected in 35 patients (44%). Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%). In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04), male gender (p < 0.001) and abnormal ECG (p < 0.001). Disease duration, CTG repeat length, severity of neuromuscular symptoms and NT-proBNP level did not predict the presence of myocardial abnormalities. CONCLUSIONS: CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.

Evaluation of the electrocardiogram in identifying and quantifying lateral involvement in nonanterior wall infarction using cardiovascular magnetic resonance imaging.

PURPOSE: The objective of this study was to assess the involvement and extent of lateral wall myocardial infarction (MI) in patients with a first nonanterior wall MI, as reflected by changes in precordial leads. Delayed enhancement cardiac magnetic resonance imaging was used as a gold standard to localize and quantify myocardial scar tissue. METHODS: Electrocardiogram and cardiac magnetic resonance were studied in 56 patients. Areas involved were related to QRS changes in precordial leads. RESULTS: Significant correlations were found between lateral wall involvement and R waves in V(1) and V(6) (P = 0.009-0.022). For patients with circumflex branch occlusions, the MI size of the apical and lateral segments correlated strongly with the characteristics of R waves in V(1) and V(2) (P = 0.001-0.034). CONCLUSIONS: Tall and broad R waves in V(1) reflect lateral wall MI, especially in circumflex occlusions.

Association between comorbidities and left and right atrial dysfunction in patients with paroxysmal atrial fibrillation: Analysis of AF-RISK.

BACKGROUND: To identify the association between comorbidities and left atrial (LA) and right atrial (RA) function in patients with paroxysmal atrial fibrillation (AF). METHODS: This is a cross-sectional study. Speckle-tracking echocardiography was performed in 344 patients with paroxysmal AF at baseline, and available in 298 patients after 1-year follow-up. The number of comorbidities (hypertension, diabetes mellitus, coronary artery disease, body mass index > 25 kg/m2, age > 65 years, moderate to severe mitral valve regurgitation and kidney dysfunction (estimated glomerular filtration rate < 60 ml/min/1.73 m2)) was determined and the association with atrial strain was tested. RESULTS: Mean age of the patients was 58 (SD 12) years and 137 patients were women (40%). Patients with a higher number of comorbidities had larger LA volumes (p for trend <0.001), and had a decrease in all strain phases from the LA and RA, except for the RA contraction phase (p for trend 0.47). A higher number of comorbidities was associated with LA reservoir and conduit strain decrease independently of LA volume (p < 0.001, p < 0.001 respectively). Patients with 1-2 comorbidities, but not patients with 3 or more comorbidities, showed a further progression of impaired LA and RA function in almost all atrial strain phases at 14 [13-17] months follow-up. CONCLUSIONS: In patients with paroxysmal AF, individual and combined comorbidities are related to lower LA and RA strain. In patients with few comorbidities, impairment in atrial function progresses during one year of follow-up. Whether comorbidity management prevents or reverses decrease in atrial function warrants further study.

Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data.

BACKGROUND: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction. OBJECTIVES: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification. METHODS: Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years). RESULTS: In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005). CONCLUSIONS: Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to traditional risk models. They may improve patient selection for novel interventions, thereby enabling precision medicine.