Reduced dynamic changes in pulmonary artery compliance during isometric handgrip exercise in patients with heart failure.

Exercise intolerance is a debilitating symptom in heart failure (HF), adversely affecting both quality of life and long-term prognosis. Emerging evidence suggests that pulmonary artery (PA) compliance may be a contributing factor. This study aims to non-invasively assess PA compliance and its dynamic properties during isometric handgrip (HG) exercise in HF patients and healthy controls, using cardiovascular magnetic resonance (CMR). We prospectively enrolled 36 subjects, comprising 17 HF patients (NYHA class II and III) and 19 healthy controls. Participants performed an HG test, and we assessed changes in PA compliance and hemodynamic flow parameters using advanced CMR techniques. We also explored the relationship between CMR-derived PA compliance metrics and established clinical indicators, ensuring the validity of our findings through intra- and interobserver agreements. HF patients had significantly lower resting PA compliance compared to controls (28.9% vs. 50.1%, p < 0.01). During HG exercise, HF patients exhibited a dampened adaptability in PA compliance. Hemodynamic responses, including heart rate and blood pressure, were not significantly different between the groups. Further analyses revealed a significant correlation between changes in PA compliance and functional capacity, and an inverse relationship with NYHA class. Our study demonstrates a marked difference in PA vascular responses during HG exercise between HF patients and healthy controls. The compromised adaptability in PA compliance in HF patients is correlated with diminished functional capacity. These findings have significant clinical implications and may guide future interventional strategies in HF management.

Analysis of acute COVID-19 including chronic morbidity: protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP).

BACKGROUND: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). METHODS: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. RESULTS: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. CONCLUSION: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.

Half-Dose versus Single-Dose Gadobutrol for Extracellular Volume Measurements in Cardiac Magnetic Resonance.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging with gadolinium-based contrast agents offers unique non-invasive insights into cardiac tissue composition. Myocardial extracellular volume (ECV) has evolved as an objective and robust parameter with broad diagnostic and prognostic implications. For the gadolinium compound gadobutrol, the recommended dose for cardiac imaging, including ECV measurements, is 0.1 mmol/kg (single dose). This dose was optimized for late enhancement imaging, a measure of focal fibrosis. Whether a lower dose is sufficient for ECV measurements is unknown. We aim to evaluate the accuracy of ECV measurements using a half dose of 0.05 mmol/kg gadobutrol compared to the standard single dose of 0.1 mmol/kg. METHODS AND RESULTS: From a contemporary trial (NCT04747366, registered 10 February 2021), a total of 25 examinations with available T1 mapping before and after 0.05 and 0.1 mmol/kg gadobutrol were analyzed. ECV values were calculated automatically from pre- and post-contrast T1 relaxation times. T1 and ECV Measurements were performed in the midventricular septum. ECV values after 0.05 and 0.1 mmol/kg gadobutrol were correlated (R2 = 0.920, p < 0.001). ECV values after 0.05 mmol/kg had a bias of +0.9% (95%-CI [0.4; 1.4], p = 0.002) compared to 0.1 mmol/kg gadobutrol, with limits of agreement from -1.5 to 3.3%. CONCLUSIONS: CMR with a half dose of 0.05 mmol/kg gadobutrol overestimated ECV by 0.9% compared with a full dose of 0.1 mmol/kg, necessitating adjustment of normal values when using half-dose ECV imaging.

Simultaneous assessment of vascular distensibility and vessel wall area at coronary, carotid, and aortic level in diabetic patients using CMR: detection of vascular remodeling.

AIMS: No data is available about the significance of cardiovascular magnetic resonance (CMR) derived vascular distensibility (VD) and vessel wall ratio (VWR) for risk stratification in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to investigate the effects of T2DM on VD and VWR using CMR in both central and peripheral territories. METHODS: Thirty-one T2DM-patients and nine controls underwent CMR. Angulation of the aorta, the common carotid, and the coronary arteries was performed to obtain cross-sectional vessel areas. RESULTS: In T2DM the Carotid-VWR and the Aortic-VWR correlated significantly. Mean values of Carotid-VWR and Aortic-VWR were significantly higher in T2DM than in controls. Coronary-VD was significantly lower in T2DM than in controls. No significant difference in Carotid-VD or Aortic-VD in T2DM vs. controls, respectively, could be observed. In a subgroup of thirteen T2DM patients with coronary artery disease (CAD), Coronary-VD was significantly lower and Aortic-VWR was significantly higher compared to T2DM patients without CAD. CONCLUSION: CMR allows a simultaneous evaluation of the structure and function of three important vascular territories to detect vascular remodeling in T2DM.

Reduced functional capacity is associated with the proportion of impaired myocardial deformation assessed in heart failure patients by CMR.

Aims: Heart failure (HF) does not only reduce the life expectancy in patients, but their life is also often limited by HF symptoms leading to a reduced quality of life (QoL) and a diminished exercise capacity. Novel parameters in cardiac imaging, including both global and regional myocardial strain imaging, promise to contribute to better patient characterization and ultimately to better patient management. However, many of these methods are not part of clinical routine yet, their associations with clinical parameters have been poorly studied. An imaging parameters that also indicate the clinical symptom burden of HF patients would make cardiac imaging more robust toward incomplete clinical information and support the clinical decision process. Methods and results: This prospective study conducted at two centers in Germany between 2017 and 2018 enrolled stable outpatient subjects with HF [n = 56, including HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)] and a control cohort (n = 19). Parameters assessed included measures for external myocardial function, for example, cardiac index and myocardial deformation measurements by cardiovascular magnetic resonance imaging, left ventricular global longitudinal strain (GLS), the global circumferential strain (GCS), and the regional distribution of segment deformation within the LV myocardium, as well as basic phenotypical characteristics including the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the 6-minute walk test (6MWT). If less than 80% of the LV segments are preserved in their deformation capacity the functional capacity by 6MWT (6 minutes walking distance: MyoHealth ≥ 80%: 579.8 ± 177.6 m; MyoHealth 60-<80%: 401.3 ± 121.7 m; MyoHealth 40-<60%: 456.4 ± 68.9 m; MyoHealth < 40%: 397.6 ± 125.9 m, overall p-value: 0.03) as well as the symptom burden are significantly impaired (NYHA class: MyoHealth ≥ 80%: 0.6 ± 1.1 m; MyoHealth 60-<80%: 1.7 ± 1.2 m; MyoHealth 40-<60%: 1.8 ± 0.7 m; MyoHealth < 40%: 2.4 ± 0.5 m; overall p-value < 0.01). Differences were also observed in the perceived exertion assessed by on the Borg scale (MyoHealth ≥ 80%: 8.2 ± 2.3 m; MyoHealth 60-<80%: 10.4 ± 3.2 m; MyoHealth 40-<60%: 9.8 ± 2.1 m; MyoHealth < 40%: 11.0 ± 2.9 m; overall p-value: 0.20) as well as quality of life measures (MLHFQ; MyoHealth ≥ 80%: 7.5 ± 12.4 m; MyoHealth 60-<80%: 23.4 ± 23.4 m; MyoHealth 40-<60%: 20.5 ± 21.2 m; MyoHealth < 40%: 27.4 ± 24.4 m; overall p-value: 0.15)-while these differences were not significant. Conclusion: The share of LV segments with preserved myocardial contraction promises to discriminate between symptomatic and asymptomatic subjects based on the imaging findings, even when the LV ejection fraction is preserved. This finding is promising to make imaging studies more robust toward incomplete clinical information.

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

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

Brief Research Report: Quantitative Analysis of Potential Coronary Microvascular Disease in Suspected Long-COVID Syndrome.

Background: Case series have reported persistent cardiopulmonary symptoms, often termed long-COVID or post-COVID syndrome, in more than half of patients recovering from Coronavirus Disease 19 (COVID-19). Recently, alterations in microvascular perfusion have been proposed as a possible pathomechanism in long-COVID syndrome. We examined whether microvascular perfusion, measured by quantitative stress perfusion cardiac magnetic resonance (CMR), is impaired in patients with persistent cardiac symptoms post-COVID-19. Methods: Our population consisted of 33 patients post-COVID-19 examined in Berlin and London, 11 (33%) of which complained of persistent chest pain and 13 (39%) of dyspnea. The scan protocol included standard cardiac imaging and dual-sequence quantitative stress perfusion. Standard parameters were compared to 17 healthy controls from our institution. Quantitative perfusion was compared to published values of healthy controls. Results: The stress myocardial blood flow (MBF) was significantly lower [31.8 ± 5.1 vs. 37.8 ± 6.0 (µl/g/beat), P < 0.001] and the T2 relaxation time was significantly higher (46.2 ± 3.6 vs. 42.7 ± 2.8 ms, P = 0.002) post-COVID-19 compared to healthy controls. Stress MBF and T1 and T2 relaxation times were not correlated to the COVID-19 severity (Spearman r = -0.302, -0.070, and -0.297, respectively) or the presence of symptoms. The stress MBF showed a U-shaped relation to time from PCR to CMR, no correlation to T1 relaxation time, and a negative correlation to T2 relaxation time (Pearson r = -0.446, P = 0.029). Conclusion: While we found a significantly reduced microvascular perfusion post-COVID-19 compared to healthy controls, this reduction was not related to symptoms or COVID-19 severity.

Case Series of Potential Cardiac Inflammation Associated With Various SARS-CoV-2 Vaccinations Assessed by Cardiac MRI.

Serious adverse events associated with new vaccines targeting SARS-CoV-2 are of high interest to the public and to public health as a worldwide mass immunization campaign has been initiated to contain the ongoing COVID-19 pandemic. We describe a series of 4 individuals with signs of a myocarditis/pericarditis according to cardiac MRI results in temporal association with currently in the European Union authorized SARS-CoV-2 vaccines. We found mild abnormal MRI results independent of the type of SARS-CoV-2 vaccine. There is a need of continuing monitoring outcomes of myocarditis cases after COVID-19 vaccination as recently published cases suggest an uncomplicated short-term course whereas the long-term implications are not yet known but taking the available evidence into account the benefits of using COVID-19 vaccines still clearly outweigh the risks.

Synthetic Extracellular Volume in Cardiac Magnetic Resonance Without Blood Sampling: a Reliable Tool to Replace Conventional Extracellular Volume.

BACKGROUND: The calculation of extracellular volume (ECV) in cardiac magnetic resonance requires hematocrit, limiting its applicability in clinical practice. Based on the linear relationship between hematocrit and blood T1 relaxivity, a synthetic ECV could be estimated without a blood sample. We aim to develop and test regression models for synthetic ECV without blood sampling in 1.5-T and 3.0-T scanners. METHODS: A total of 1101 subjects who underwent cardiac magnetic resonance scanning with native and postcontrast T1 mapping and venous hematocrit within 24 hours were retrospectively enrolled. Subjects were randomly split into derivation (n=550) and validation (n=551) subgroups for each scanner. Different regression models were derived controlling for sex, field strength, and left ventricle/right ventricle blood pool and validated in the validation group. We performed additional validation analyses in subgroups of patients with histological validation (n=17), amyloidosis (n=29), anemia (n=185), and reduced ejection fraction (n=322). RESULTS: In the derivation group, 8 specific models and 2 common estimate models were derived. In the validation group, using specific models, synthetic ECV had high agreement with conventional ECV (R2, 0.87; P<0.0001 and R2, 0.88, P<0.0001; -0.16% and -0.10%, left ventricle and right ventricle model, respectively). Common models also performed well (R2, 0.88; P<0.0001 and R2, 0.89, P<0.0001; -0.21% and -0.18%, left ventricle and right ventricle model, respectively). Histological validation demonstrated equal performance of synthetic and measured ECV. Synthetic ECV as calculated by the common model showed a bias in the anemia cohort significantly reduced by the specific model (-2.45 to -1.28, right ventricle common and specific model, respectively). CONCLUSIONS: Synthetic ECV provided a promising way to calculate ECV without blood sampling. Specific models could provide the most accurate value, while common models could be more suitable in routine clinical practice because of their simplicity while maintaining adequate accuracy.

Long-term prognostic value of vasodilator stress cardiac magnetic resonance in patients with atrial fibrillation.

AIMS: Although the prevalence of coronary artery disease (CAD) is high among patients with atrial fibrillation (AF), studies on stress perfusion cardiac magnetic resonance (CMR) imaging frequently exclude patients with AF, and its prognostic and diagnostic value in high-risk patients with suspected or known CAD remains unclear. METHODS AND RESULTS: In this longitudinal cohort study, we included 164 consecutive patients with AF during vasodilator perfusion CMR. Diagnostic value was evaluated regarding invasive coronary angiography in a subset of patients. We targeted a follow-up of >5 years and used CMR results as stratification, and the primary outcome was major adverse cardiac events [MACE, cardiovascular (CV) death and myocardial infarction (MI)]. Secondary outcomes included late coronary revascularization or stroke and the components of the primary outcome. Of the whole cohort (73.8% male, mean age 72.2 years ± 7.8 SD), 99.4% were successfully scanned (163/164 patients). Median CHA2DS2-VASc score was 4 [interquartile range (IQR) 3-5], and median 10-year risk for CV events based on SMART risk score was high (24%, IQR 16-32%). Thirty-two patients (19.6%) presented with ischaemia and 52 patients (31.9%) with late gadolinium enhancement (LGE). A combination of LGE and inducible ischaemia was present in 20 patients (12.3%). Diagnostic accuracy was 86.2% [confidence interval (CI) 68.3-96.1%]. The median follow-up was 6.6 years (IQR 3.6-7.8). Ischaemia in vasodilator perfusion CMR was significantly associated with the occurrence of MACE [P < 0.01; hazard ratio (HR) 2.65, CI 1.39-5.08], as well as LGE (P = 0.03; 1.74, CI 1.07-3.64) and the combination of both (P < 0.01; HR 2.67, CI 1.59-5.62). After adjustment by age, left ventricular ejection fraction, and the presence of diabetes, ischaemia in vasodilator perfusion CMR remained significantly associated with the occurrence of MACE (2.10, CI 1.08-4.10; P = 0.03). In secondary endpoint analysis, there was a significant association of ischaemia in CMR with CV death (P < 0.05; HR 1.93, CI 0.95-3.9) and MI (P < 0.01; HR 13, CI 1.35-125.4), while no significant association was found regarding the occurrence of revascularization (P = 0.45; HR 1.43, CI 0.57-3.58) or stroke (P = 0.99; HR 0.99, CI 0.21-2.59). CONCLUSIONS: Vasodilator stress perfusion CMR demonstrated an excellent diagnostic and significant prognostic value at long-term follow-up in high-risk patients with persistent AF and suspected or known CAD.

CMR detects decreased myocardial deformation in asymptomatic patients at risk for heart failure.

Aims: The main management strategy of heart failure with preserved ejection fraction (HFpEF) is prevention since HFpEF is associated with many cardiovascular (CV) risk factors, especially since HFpEF is linked to a high risk for both mortality and recurrent heart failure (HF) hospitalizations. Therefore, there is a need for new tools to identify patients with a high risk profile early. Regional strain assessment by CMR seems to be superior in describing deformation impairment in HF. The MyoHealth score is a promising tool to identify cardiac changes early. Methods and results: Heart failure patients irrespective of LVEF and asymptomatic controls were recruited, and CMR based measures were obtained. For this analysis the asymptomatic control group (n = 19) was divided into asymptomatic subjects without CV co-morbidities or evidence of cardiac abnormalities and (n = 12) and asymptomatic subjects with CV co-morbidities or evidence of cardiac abnormalities (n = 7) as well as patients with HFpEF (n = 19). We performed CMR scans at rest and during a stress test using isometric handgrip exercise (HG). Assessing the MyoHealth score at rest revealed preserved regional strain in 85 ± 9% of LV segments in controls, 73 ± 11% in at Risk subjects and 73 ± 8% in HFpEF patients. During stress the MyoHealth score was 84 ± 7% in controls, 83 ± 7 in at risk subjects and 74 ± 11 in HFpEF patients. Conclusion: In summary, we show for the first time that asymptomatic subjects with increased CV risk present with HFpEF like impaired myocardial deformation at rest, while they show results like controls under HG stress. The potential of preventive treatment in this group of patients merits further investigation in future. Clinical trial registration: [https://drks.de/search/de/trial/DRKS00015615], identifier [DRKS00015615].

CMR findings after COVID-19 and after COVID-19-vaccination-same but different?

Cardiac involvement has been described in varying proportions of patients recovered from COVID-19 and proposed as a potential cause of prolonged symptoms, often described as post-COVID or long COVID syndrome. Recently, cardiac complications have been reported from COVID-19 vaccines as well. We aimed to compare CMR-findings in patients with clinical cardiac symptoms after COVID-19 and after vaccination. From May 2020 to May 2021, we included 104 patients with suspected cardiac involvement after COVID-19 who received a clinically indicated cardiac magnetic resonance (CMR) examination at a high-volume center. The mean time from first positive PCR to CMR was 112 ± 76 days. During their COVID-19 disease, 21% of patients required hospitalization, 17% supplemental oxygen and 7% mechanical ventilation. In 34 (32.7%) of patients, CMR provided a clinically relevant diagnosis: Isolated pericarditis in 10 (9.6%), %), acute myocarditis (both LLC) in 7 (6.7%), possible myocarditis (one LLC) in 5 (4.8%), ischemia in 4 (3.8%), recent infarction in 2 (1.9%), old infarction in 4 (3.8%), dilated cardiomyopathy in 3 (2.9%), hypertrophic cardiomyopathy in 2 (1.9%), aortic stenosis, pleural tumor and mitral valve prolapse each in 1 (1.0%). Between May 2021 and August 2021, we examined an additional 27 patients with suspected cardiac disease after COVID-19 vaccination. Of these, CMR provided at least one diagnosis in 22 (81.5%): Isolated pericarditis in 4 (14.8%), acute myocarditis in 9 (33.3%), possible myocarditis (acute or subsided) in 6 (22.2%), ischemia in 3 (37.5% out of 8 patients with stress test), isolated pericardial effusion (> 10 mm) and non-compaction-cardiomyopathy each in 1 (3.7%). The number of myocarditis diagnoses after COVID-19 was highly dependent on the stringency of the myocarditis criteria applied. When including only cases of matching edema and LGE and excluding findings in the right ventricular insertion site, the number of cases dropped from 7 to 2 while the number of cases after COVID-19 vaccination remained unchanged at 9. While myocarditis is an overall rare side effect after COVID-19 vaccination, it is currently the leading cause of myocarditis in our institution due to the large number of vaccinations applied over the last months. Contrary to myocarditis after vaccination, LGE and edema in myocarditis after COVID-19 often did not match or were confined to the RV-insertion site. Whether these cases truly represent myocarditis or a different pathological entity is to be determined in further studies.

Cardiovascular magnetic resonance findings in non-hospitalized paediatric patients after recovery from COVID-19.

AIMS: Our study aimed to investigate the cardiac involvement with sensitive tissue characterization in non-hospitalized children with coronavirus disease 2019 (COVID-19) infection using cardiovascular magnetic resonance (CMR) imaging. METHODS AND RESULTS: We prospectively enrolled children who recovered from mildly symptomatic COVID-19 infection between November 2020 and January 2021. Patients underwent CMR at 1.5 T (Achieva, Philips Healthcare, Best, the Netherlands) including cine images, native T1 and T2 mapping. Healthy children and paediatric patients with biopsy-proven myocarditis served as control groups. We performed CMR in 18 children with a median (25th-75th percentile) age of 12 (10-15) years, 38 (24-47) days after positive PCR test, and compared them with 7 healthy controls [15 (10-19) years] and 9 patients with myocarditis [10 (4-16) years]. The COVID-19 patients reported no cardiac symptoms. None of the COVID-19 patients showed CMR findings consistent with a myocarditis. Three patients (17%) from the COVID-19 cohort presented with minimal pericardial effusion. CMR parameters of COVID-19 patients, including volumetric and strain values as well as T1 and T2 times, were not significantly different from healthy controls, but from myocarditis patients. These had significantly reduced left ventricular (LV) ejection fraction (P = 0.035), LV global longitudinal strain, and left atrial strain values as well as elevated native T1 values compared with COVID-19 patients (P < 0.001, respectively). CONCLUSIONS: There was no evidence of myocardial inflammation, fibrosis, or functional cardiac impairment in the studied cohort of children recently. CMR findings were comparable with those of healthy controls. Pericardial effusion suggests a mild pericarditis in a small subgroup. This is pointing to a minor clinical relevance of myocardial involvement in children after mildly symptomatic COVID-19 infections.

Cardiac Magnetic Resonance Reveals Incipient Cardiomyopathy Traits in Adult Patients With Phenylketonuria.

Background Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collateral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. Methods and Results Thirty-nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10-year mean phenylalanine concentration, 924±330 µmol/L) and 39 age- and sex-matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten-year mean plasma levels of phenylalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end-diastolic thickness, 7.0±17 versus 8.8±1.7 mm [P<0.001]; lateral thickness, 6.1±1.4 versus 6.8±1.2 mm [P=0.004]), more dilated left ventricular cavity (end-diastolic volume, 87±14 versus 80±14 mL/m2 [P=0.0178]; end-systolic volume, 36±9 versus 29±8 mL/m2 [P<0.001]), lower ejection fraction (59±6% versus 64±6% [P<0.001]), reduced systolic deformation (global circumferential strain, -29.9±4.2 % versus -32.2±5.0 % [P=0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m2 [P<0.001]). T1 native values were decreased (936±53 versus 996±26 ms [P<0.001]), with particular low values in patients with phenylalanine >1200 µmol/L (909±48 ms). Both mean phenylalanine (P=0.013) and tyrosine (P=0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. Conclusions Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early-stage cardiomyopathy. Regular cardiology follow-up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipidemia, are recommended.

Late onset apical hypertrophic cardiomyopathy: a case report.

BACKGROUND: Apical hypertrophic cardiomyopathy provides diagnostic challenges through varying presentation, impaired visualization on echocardiography and dissent on diagnostic criteria. While hypertrophic cardiomyopathy in general requires an absolute wall thickness ≥15 mm, a threshold for relative apical hypertrophy (ratio 1.5) has been proposed. CASE SUMMARY: We report the case of a 57-year-old man with newly arisen chest pain and slight T-wave inversions. Serial cardiac magnetic resonance imaging over 9 years documented the gradual evolvement of late-onset apical hypertrophy with apical fibrosis and strain abnormalities. Symptoms, electrocardiographic changes, and relative apical hypertrophy preceded the traditional imaging criteria of hypertrophic cardiomyopathy. DISCUSSION: Relative apical hypertrophy can be an early manifestation of apical hypertrophic cardiomyopathy. Persistent cardiac signs and symptoms warrant a follow-up, as apical hypertrophic cardiomyopathy can evolve over time. Cardiac magnetic resonance imaging readily visualizes apical hypertrophic cardiomyopathy and associated changes in tissue composition and function.

Myocardial deformation assessed among heart failure entities by cardiovascular magnetic resonance imaging.

AIMS: Although heart failure (HF) is a leading cause for hospitalization and mortality, normalized and comparable non-invasive assessment of haemodynamics and myocardial action remains limited. Moreover, myocardial deformation has not been compared between the guideline-defined HF entities. The distribution of affected and impaired segments within the contracting left ventricular (LV) myocardium have also not been compared. Therefore, we assessed myocardial function impairment by strain in patients with HF and control subjects by magnetic resonance imaging after clinically phenotyping these patients. METHODS AND RESULTS: This prospective study conducted at two centres in Germany between 2017 and 2018 enrolled stable outpatient subjects with HF [n = 56, including HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)] and a control cohort (n = 12). Parameters assessed included measures for external myocardial function, for example, cardiac index and myocardial deformation measurements by cardiovascular magnetic resonance imaging, left ventricular global longitudinal strain (GLS), the global circumferential strain (GCS) and the regional distribution of segment deformation within the LV myocardium, as well as basic phenotypical characteristics. Comparison of the cardiac indices at rest showed no differences neither between the HF groups nor between the control group and HF patients (one-way ANOVA P = 0.70). The analysis of the strain data revealed differences between all groups in both LV GLS (One-way ANOVA: P < 0.01. Controls vs. HFpEF: -20.48 ± 1.62 vs. -19.27 ± 1.25. HFpEF vs. HFmrEF: -19.27 ± 1.25 vs. -15.72 ± 2.76. HFmrEF vs. HFrEF: -15.72 ± 2.76 vs. -11.51 ± 3.97.) and LV GCS (One-way ANOVA: P < 0.01. Controls vs. HFpEF: -19.74 ± 2.18 vs. -17.47 ± 2.10. HFpEF vs. HFmrEF: -17.47 ± 2.10 vs. -12.78 ± 3.47. HFrEF: -11.41 ± 3.27). Comparing the segment deformation distribution patterns highlighted the discriminating effect between the groups was much more prominent between the groups (one-way ANOVA P < 0.01) when compared by a score combining regional effects and a global view on the LV. Further analyses of the patterns among the segments affected showed that while the LVEF is preserved in HFpEF, the segments impaired in their contractility are located in the ventricular septum. The worse the LVEF is, the more segments are affected, but the septum remains an outstanding location with the most severe contractility impairment throughout the HF entities. CONCLUSIONS: While cardiac index at rest did not differ significantly between controls and stable HF patients suffering from HFrEF, HFmrEF, or HFpEF, the groups did differ significantly in LV GLS and LV GCS values. Regional strain analysis revealed that the LV septum is the location affected most, with reduced values already visible in HFpEF and further reductions in HFmrEF and HFrEF.

COVID-19 vs. Classical Myocarditis Associated Myocardial Injury Evaluated by Cardiac Magnetic Resonance and Endomyocardial Biopsy.

Background: Despite the ongoing global pandemic, the impact of COVID-19 on cardiac structure and function is still not completely understood. Myocarditis is a rare but potentially serious complication of other viral infections with variable recovery, and is, in some cases, associated with long-term cardiac remodeling and functional impairment. Aim: To assess myocardial injury in patients who recently recovered from an acute SARS-CoV-2 infection with advanced cardiac magnetic resonance imaging (CMR) and endomyocardial biopsy (EMB). Methods: In total, 32 patients with persistent cardiac symptoms after a COVID-19 infection, 22 patients with acute classic myocarditis not related to COVID-19, and 16 healthy volunteers were included in this study and underwent a comprehensive baseline CMR scan. Of these, 10 patients post COVID-19 and 13 with non-COVID-19 myocarditis underwent a follow-up scan. In 10 of the post-COVID-19 and 15 of the non-COVID-19 patients with myocarditis endomyocardial biopsy (EMB) with histological, immunohistological, and molecular analysis was performed. Results: In total, 10 (31%) patients with COVID-19 showed evidence of myocardial injury, eight (25%) presented with myocardial oedema, eight (25%) exhibited global or regional systolic left ventricular (LV) dysfunction, and nine (28%) exhibited impaired right ventricular (RV) function. However, only three (9%) of COVID-19 patients fulfilled updated CMR-Lake Louise criteria (LLC) for acute myocarditis. Regarding EMB, none of the COVID-19 patients but 87% of the non-COVID-19 patients with myocarditis presented histological findings in keeping with acute or chronic inflammation. COVID-19 patients with severe disease on the WHO scale presented with reduced biventricular longitudinal function, increased RV mass, and longer native T1 times compared with those with only mild or moderate disease. Conclusions: In our cohort, CMR and EMB findings revealed that SARS-CoV-2 infection was associated with relatively mild but variable cardiac involvement. More symptomatic COVID-19 patients and those with higher clinical care demands were more likely to exhibit chronic inflammation and impaired cardiac function compared to patients with milder forms of the disease.