Karl-Philipp Rommel

Comprehensive Cardiac Magnetic Resonance Imaging in Patients With Suspected Myocarditis: The MyoRacer-Trial.

BACKGROUND Data suggest that T1 and T2 mapping have excellent diagnostic accuracy in patients with suspected myocarditis. However, the true diagnostic performance of comprehensive cardiac magnetic resonance (CMR) mapping versus endomyocardial biopsy (EMB) has not been determined. OBJECTIVES This study assessed the performance of CMR imaging, including T1 and T2 mapping, compared with EMB in an unselected, consecutive patient cohort with suspected myocarditis. It also examined the potential role of CMR field strength by comparing 1.5-T versus 3.0-T imaging. METHODS Patients underwent biventricular EMB, cardiac catheterization (for exclusion of coronary artery disease), and CMR imaging on 1.5- and 3-T scanners. The CMR protocol included current standard Lake Louise criteria (LLC) for myocarditis as well as native T1, calculation of extracellular volume fraction (ECV), and T2 mapping (only on 1.5-T). Patients were divided into 2 groups according to symptom duration (acute: ≤14 days vs. chronic: >14 days). RESULTS A total of 129 patients underwent 1.5-T imaging. In patients with acute symptoms, native T1 yielded the best diagnostic performance as defined by the area under the curve (AUC) of receiver-operating curves (0.82) followed by T2 (0.81), ECV (0.75), and LLC (0.56). In patients with chronic symptoms, only T2 mapping yielded an acceptable AUC (0.77). On 3.0-T, AUCs of native T1, ECV, and LLC were comparable to 1.5-T with no significant differences. CONCLUSIONS In patients with acute symptoms, mapping techniques provide a useful tool for confirming or rejecting the diagnosis of myocarditis and are superior to the LLC. However, only T2 mapping has acceptable diagnostic performance in patients with chronic symptoms. (Magnetic Resonance Imaging in Myocarditis [MyoRacer]; NCT02177630).

Extracellular Volume Fraction for Characterization of Patients With Heart Failure and Preserved Ejection Fraction.

BACKGROUND Optimal patient characterization in heart failure with preserved ejection fraction (HFpEF) is essential to tailor successful treatment strategies. Cardiac magnetic resonance (CMR)-derived T1 mapping can noninvasively quantify diffuse myocardial fibrosis as extracellular volume fraction (ECV). OBJECTIVES This study aimed to elucidate the diagnostic performance of T1 mapping in HFpEF by examining the relationship between ECV and invasively measured parameters of diastolic function. It also investigated the potential of ECV to differentiate among pathomechanisms in HFpEF. METHODS We performed T1 mapping in 24 patients with HFpEF and 12 patients without heart failure symptoms. Pressure-volume loops were obtained with a conductance catheter during basal conditions and handgrip exercise. Transient pre-load reduction was used to extrapolate the diastolic stiffness constant. RESULTS Patients with HFpEF showed higher ECV (p < 0.01), elevated load-independent passive left ventricular (LV) stiffness constant (beta) (p < 0.001), and a longer time constant of active LV relaxation (p = 0.02). ECV correlated highly with beta (r = 0.75; p < 0.001). Within the HFpEF cohort, patients with ECV greater than the median showed a higher beta (p = 0.05), whereas ECV below the median identified patients with prolonged active LV relaxation (p = 0.01) and a marked hypertensive reaction to exercise due to pathologic arterial elastance (p = 0.04). On multiple linear regression analyses, ECV independently predicted intrinsic LV stiffness (β = 0.75; p < 0.01). CONCLUSIONS Diffuse myocardial fibrosis, assessed by CMR-derived T1 mapping, independently predicts invasively measured LV stiffness in HFpEF. Additionally, ECV helps to noninvasively distinguish the role of passive stiffness and hypertensive exercise response with impaired active relaxation. (Left Ventricular Stiffness vs. Fibrosis Quantification by T1 Mapping in Heart Failure With Preserved Ejection Fraction [STIFFMAP]; NCT02459626).

Endomyocardial miR-133a levels correlate with myocardial inflammation, improved left ventricular function, and clinical outcome in patients with inflammatory cardiomyopathy

Inflammatory heart disease represents an important cause of chronic dilated cardiomyopathy (DCM). Predicting the clinical course of patients with inflammatory cardiomyopathy (iCMP) is difficult, and the prognostic value of current biological markers remains controversial. We tested whether expression of selected microRNAs in endomyocardial biopsies (EMBs) is related to LV functional recovery and clinical events in iCMP patients.

Biventricular endomyocardial biopsy in patients with suspected myocarditis: Feasibility, complication rate and additional diagnostic value

BACKGROUND Previous retrospective analyses have suggested that biventricular (BV) endomyocardial biopsy (EMB) is superior compared to selective left ventricular (LV) or right ventricular (RV) EMB. This study prospectively assessed the feasibility, safety and diagnostic performance of implementing a routine BV-EMB approach in patients with suspected myocarditis. METHODS Consecutive patients with clinically suspected myocarditis underwent EMB (n=136). Myocarditis was defined as ≥14 infiltrating leukocytes/mm2 in addition to enhanced human leukocyte antigen class II expression in professional antigen-presenting immune cells. The presence of viral genomes was assessed by nested (reverse transcriptase-) polymerase chain reaction. RESULTS BV-EMB was attempted in 132 patients (LV thrombus, n=3; complication during RV-EMB, n=1) and resulted in sufficient samples from both ventricles in 127 patients (96.2%). One major complication (pericardial tamponade requiring surgical revision) was observed during the 136 RV-EMB (0.7%). No severe complications occurred during the 132 LV procedures. Of the 127 patients with BV-EMB, myocarditis was diagnosed in 89 patients (70.1%). While 67 patients (75.3%) fulfilled the diagnostic criteria in both ventricles, the diagnosis of myocarditis was based on the results of LV-EMB only in 16 patients (18%) and of RV-EMB only in 6 patients (6.7%). Viral genomes were found in 45 of the 127 patients (35.4%) with evidence of virus genome only in the left ventricle in 10 patients (22.2%) and only in the right ventricle in 3 patients (6.7%). CONCLUSIONS Implementing a routine BV-EMB approach is feasible and safe. In patients with suspected myocarditis, BV-EMB yields superior diagnostic performance compared to selective RV- or LV-EMB.

ST-segment depression resolution predicts infarct size and reperfusion injury in ST-elevation myocardial infarction

Objective ST-elevation myocardial infarction (STEMI) is frequently associated with reciprocal ST-segment depression in contralateral ECG leads. However, the relationship of the resolution of ST-segment depression (STD-R) with myocardial damage is unknown and the potential prognostic value incompletely understood. We sought to evaluate the association between STD-R and markers of myocardial injury as well as to determine the prognostic impact of STD-R in patients with acute reperfused STEMI. Methods We enrolled 611 patients with STEMI in this multicentre cardiac magnetic resonance (CMR) study. STD-R, defined as either worsened (<0%), incomplete (0–50%) or complete (≥50%), was determined 90 min after primary percutaneous coronary intervention (PCI). Patients underwent CMR in median 3 (2–4) days after infarction. Major adverse cardiac events (MACE) were defined as a composite of death, reinfarction and new congestive heart failure within 12 months after enrolment. Results Patients with worsened or incomplete STD-R (n=148 (24.2%)) had a significantly larger area at risk (42 (31–50) vs 37 (29–52) vs 34 (24–46) %LV, p=0.001), larger infarct size (20 (13–30) vs 17(10–26) vs 16 (8–24) %LV, p=0.003), larger extent of microvascular obstruction (0.6(0–3.4) vs 0.4 (0–2.4) vs 0.0 (0–1.4) %LV, p=0.003), and a lower LVEF (46 (39–54) vs 48 (40–56) vs 52 (45–58) %, p<0.001). MACE rate (n=37 (6%)) was significantly higher in patients with worsened (n=10 (19%)) or incomplete STD-R (n=7 (7%)) than in patients with complete STD-R (n=20 (4%), p<0.001). In multivariate Cox regression analysis, categorised STD-R emerged as an independent predictor of MACE at 12 months after adjusting for clinical variables (p=0.007). Conclusions Patients with acute STEMI and worsened or incomplete STD-R after PCI show a more pronounced myocardial as well as microvascular damage as detected by CMR with subsequent independent prognostic information on MACE over a 12-month follow-up period.

QRS complex distortion (Grade 3 ischaemia) as a predictor of myocardial damage assessed by cardiac magnetic resonance imaging and clinical prognosis in patients with ST-elevation myocardial infarction

AIMS Distortion of the terminal portion of the QRS complex (so-called Grade 3 ischaemia, G3I) has been associated with adverse outcomes in ST-elevation myocardial infarction (STEMI) populations. However, the correlation of G3I with infarct size and microvascular injury as defined by cardiac magnetic resonance (CMR) is not well defined. Aim of this study was to assess the relation of G3I with myocardial damage as assessed by CMR and clinical outcomes in STEMI patients. METHODS AND RESULTS We analysed the ECGs of 572 consecutive STEMI patients regarding the presence or absence of G3I. CMR was performed within 1 week after infarction for comprehensive assessment of myocardial damage using a standardized protocol. The primary clinical endpoint was major adverse cardiac events (MACE) within 12 months after infarction. G3I was present in 186 (32%) patients. The presence of G3I was associated with larger infarct size (P = 0.01), the presence of late microvascular obstruction (P = 0.05), the presence of intramyocardial haemorrhage (P = 0.04), and impaired myocardial salvage (P = 0.01). G3I was associated with a higher incidence of MACE (P = 0.01) and was identified as an independent predictor of MACE in Cox regression analysis (HR 2.19; 95% CI 1.10 to 4.38, P = 0.03). CONCLUSION This largest study to date correlating G3I on the admission ECG with CMR markers of myocardial damage demonstrates that G3I is significantly associated with infarct size, impaired myocardial salvage, and reperfusion injury in a reperfused STEMI population. Moreover, G3I was independently associated with MACE. CLINICALTRIALS.GOV: NCT00712101.

Management of arrhythmias in patients with Takotsubo cardiomyopathy: Is the implantation of permanent devices necessary?

BACKGROUND Arrhythmias are frequent in Takotsubo cardiomyopathy (TTC) and a major determinant of outcome. OBJECTIVE The purpose of this study was to provide a rationale for management strategies, particularly for permanent device implantation given the reversible nature of TTC. METHODS Treatment strategies of arrhythmias including ventricular fibrillation (VF), ventricular tachycardia (VT), asystole, pulseless electrical activity, and complete atrioventricular (AV) or sinoatrial block were assessed in a bicentric cohort of consecutive patients with TTC (n = 286) with a mean follow-up period of 3.3 ± 2.4 years. RESULTS The prevalence of arrhythmias during the acute phase of TTC was 12.2% (n = 35), consisting predominantly of VT (n = 16 [5.6%]), VF (n = 7 [2.4%]), and complete AV block (n = 8 [2.8%]). Seven patients received a permanent pacemaker because of complete AV (n = 6) or sinoatrial (n = 1) block. Regular device checkups were available in 2 patients and demonstrated ongoing high-degree AV block despite recovery of left ventricular function. Three patients with transient bradyarrhythmias who did not receive devices died shortly after hospital discharge from unknown causes. One patient received an implantable cardioverter-defibrillator after resuscitation for VF and did not require device interventions during 2-year follow-up. Patients with polymorphic VT (n = 7), monomorphic VT (n = 6), or VF (n = 2) who were discharged from hospital survived or died of noncardiac reasons, with the cause of death remaining unclear in 1 patient with monomorphic sustained VT. CONCLUSION Our data suggest that bradyarrhythmias in the acute setting of TTC may require permanent pacemaker implantation. In contrast, polymorphic ventricular arrhythmias might be managed with a temporary approach (eg, wearable cardioverter-defibrillators) until recovery of repolarization time and left ventricular function.

Influence of Left Atrial Function on Exercise Capacity and Left Ventricular Function in Patients With Heart Failure and Preserved Ejection FractionCLINICAL PERSPECTIVE

Background— Although left atrial (LA) dysfunction is common in heart failure with preserved ejection fraction (HFpEF), its functional implications beyond the reflection of left ventricular (LV) pathology are not well understood. The aim of this study was to further characterize LA function in HFpEF patients. Methods and Results— We performed cardiac magnetic resonance myocardial feature tracking in 22 patients with HFpEF and 12 patients without HFpEF. LA reservoir strain, LA conduit strain, and LA booster pump strain were quantified. Peak oxygen uptake (VO2max) was determined. Invasive pressure–volume loops were obtained to evaluate LV diastolic properties. LV early filling was determined from LV volume–time curves as derived from cardiac magnetic resonance. LA reservoir and conduit strain were significantly lower in HFpEF (LA reservoir strain, 22±7% versus 29±6%, P=0.04; LA conduit strain, −9±5% versus −15±4%, P<0.01). Patients with HFpEF showed lower oxygen uptake (17±6 versus 29±8 mL/(kg min); P<0.01). Strain measurement for LA conduit function was strongly associated with VO2max (r=0.80; P<0.01). On multivariable regression analysis, LA conduit strain emerged as strongest predictor for VO2max even after inclusion of LV stiffness and relaxation time (&bgr;=0.80; P<0.01). LA conduit strain correlated with the volume of early ventricular filling (r=0.67; P<0.01), but not LV stiffness constant &bgr; (−0.34; P=0.051) or relaxation constant &tgr; (r=−0.33; P=0.06). Conclusions— Cardiac magnetic resonance myocardial feature tracking–derived conduit strain is significantly impaired in HFpEF and associated with exercise intolerance. Impaired conduit function is associated with impaired early ventricular filling, as potential mechanism leading to impaired oxygen uptake. Our results propose that impaired LA conduit function represents a distinct feature of HFpEF, independent of LV stiffness and relaxation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02459626.

Invasive aortic pulse wave velocity as a marker for arterial stiffness predicts outcome of renal sympathetic denervation.

AIMS A recurrent finding of trials on renal sympathetic denervation is a certain percentage of non-responders. The aim of this study was to examine the influence of arterial stiffness to predict response. METHODS AND RESULTS Eighty-eight patients were included in the study. Arterial stiffness was measured by invasive pulse wave velocity. Antihypertensive medication had to be unchanged during follow-up. Ambulatory blood pressure measurement (ABPM) was used to record blood pressure before and six months after denervation. Fifty-eight patients without changes in medication were included in the final analysis. Responders (n=37; blood pressure reduction -12.8±6.4 mmHg) had a significantly lower pulse wave velocity (14.4±4.4 m/s versus 17.7±4.5 m/s; p=0.009) compared to non-responders (n=21; blood pressure reduction +3.0±4.5 mmHg; p<0.001 for comparison with responders). In multivariate analysis, invasive pulse wave velocity was the only significant predictor of blood pressure reduction after denervation (odds ratio 1.15, 95% confidence interval [CI] 1.014-1.327; p=0.03). Patients with increased stiffness were older (p=0.001), had a higher prevalence of diabetes (p=0.008), more often had isolated systolic hypertension (p=0.007), and had a higher invasive pulse pressure (p<0.001). CONCLUSIONS Patients with lower pulse wave velocity showed a significantly better response to denervation. These findings emphasise that pulse wave velocity might be used as a selection criterion for renal denervation.

Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and FibrosisCLINICAL PERSPECTIVE: Implications for Its Use as a Biomarker

Background— Galectin (Gal)-3 is a &bgr;-galactoside-binding lectin and currently intensely studied as a biomarker in heart failure. Gal-3 also exerts proinflammatory effects, at least in extracardiac tissues. Objective of this study was to characterize the relationship of plasma and myocardial Gal-3 levels with cardiac fibrosis and inflammation in patients with nonischemic dilated cardiomyopathy and inflammatory cardiomyopathy (iCMP). Methods and Results— Endomyocardial biopsies and blood samples were obtained from patients with newly diagnosed cardiomyopathy and clinical suspicion of myocarditis. According to histopathologic findings, patients were classified as having dilated cardiomyopathy (n=40) or iCMP (n=75). Cardiac fibrosis was assessed histologically on endomyocardial biopsy sections. In patients with iCMP, myocardial Gal-3 expression significantly correlated with inflammatory cell count on endomyocardial biopsy (r=0.56; P<0.05). In contrast, an inverse association was observed between myocardial Gal-3 expression and cardiac fibrosis in patients with iCMP (r=−0.59; P<0.05). In patients with dilated cardiomyopathy, myocardial Gal-3 expression correlated with cardiac fibrosis on left ventricular biopsy (P=0.63; P<0.01). Of note, in both groups, plasma Gal-3 levels did not correlate with myocardial Gal-3 levels or left ventricular fibrosis, whereas a positive correlation between plasma Gal-3 levels and inflammatory cell count on endomyocardial biopsy was observed in patients with iCMP. Conclusions— The present study suggests that myocardial Gal-3 can be considered as a possible marker for both cardiac inflammation and fibrosis, depending on the pathogenesis of heart failure. However, circulating concentrations of Gal-3 do not seem to reflect endomyocardial Gal-3 levels or cardiac fibrosis.