Heiko Mahrholdt

2014 ESC/EACTS Guidelines on myocardial revascularization The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Authors/Task Force members: Stephan Windecker* (ESC Chairperson) (Switzerland), Philippe Kolh* (EACTS Chairperson) (Belgium), Fernando Alfonso (Spain), Jean-Philippe Collet (France), Jochen Cremer (Germany), Volkmar Falk (Switzerland), Gerasimos Filippatos (Greece), Christian Hamm (Germany), Stuart J. Head (The Netherlands), Peter Jüni (Switzerland), A. Pieter Kappetein (The Netherlands), Adnan Kastrati (Germany), Juhani Knuuti (Finland), Ulf Landmesser (Switzerland), Günther Laufer (Austria), Franz-Josef Neumann (Germany), Dimitrios J. Richter (Greece), Patrick Schauerte (Germany), Miguel Sousa Uva (Portugal), Giulio G. Stefanini (Switzerland), David Paul Taggart (UK), Lucia Torracca (Italy), Marco Valgimigli (Italy), William Wijns (Belgium), and Adam Witkowski (Poland).

Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study

BACKGROUND Myocardial infarcts are routinely detected by nuclear imaging techniques such as single photon emission computed tomography (SPECT) myocardial perfusion imaging. A newly developed technique for infarct detection based on contrast-enhanced cardiovascular magnetic resonance (CMR) has higher spatial resolution than SPECT. We postulated that this technique would detect infarcts missed by SPECT. METHODS We did contrast-enhanced CMR and SPECT examinations in 91 patients with suspected or known coronary artery disease. All CMR and SPECT images were scored, using a 14-segment model, for the presence, location, and spatial extent of infarction. To compare each imaging modality to a gold standard, we also acquired contrast-enhanced CMR and SPECT images in 12 dogs with, and three dogs without, myocardial infarction as defined by histochemical staining. FINDINGS In animals, contrast-enhanced CMR and SPECT detected all segments with nearly transmural infarction (>75% transmural extent of the left-ventricular wall). CMR also identified 100 of the 109 segments (92%) with subendocardial infarction (<50% transmural extent of the left-ventricular wall), whereas SPECT identified only 31 (28%). SPECT and CMR showed high specificity for the detection of infarction (97% and 98%, respectively). In patients, all segments with nearly transmural infarction, as defined by contrast-enhanced CMR, were detected by SPECT. However, of the 181 segments with subendocardial infarction, 85 (47%) were not detected by SPECT. On a per patient basis, six (13%) individuals with subendocardial infarcts visible by CMR had no evidence of infarction by SPECT. INTERPRETATION SPECT and CMR detect transmural myocardial infarcts at similar rates. However, CMR systematically detects subendocardial infarcts that are missed by SPECT.

2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC)

2D : two-dimensional 99mTc-DPD : 99mTechnetium-3,3-diphosphono- 1,2-propanodi-carboxylic acid ACE : angiotensin-converting enzyme AF : atrial fibrillation AL : amyloid light chain AR : aortic regurgitation ARB : angiotensin receptor blocker ATTR : amyloidosis-transthyretin type AV : atrioventricular BiVAD : biventricular assist device BNP : brain natriuretic peptide BPM : Beats per minute CCS : Canadian Cardiovascular Society CFC : cardiofacialcutaneous CHA2DS2-VASc : Congestive Heart failure, hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65–74, and Sex (female) CMR : cardiac magnetic resonance CRT : cardiac resynchronization therapy CRT-D : cardiac resynchronization therapy-defibrillator CRT-P : Cardiac resynchronization therapy with a pacemaker CT : computed tomography DC : direct current DNA : deoxyribonucleic acid E/A : ratio of mitral peak velocity of early filling (E) to mitral peak velocity of late filling (A) E/e’ : ratio of early transmitral flow velocity (E) to early mitral annulus velocity (e’) EACTS : European Association for Cardio-Thoracic Surgery ECG : electrocardiogram EF : ejection fraction EPS : electrophysiological study ESC : European Society of Cardiology FDA : (US) Food and Drug Administration FHL1 : four and a half LIM domains 1 HAS-BLED : hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly (>65 years), drugs/alcohol concomitantly HCM : hypertrophic cardiomyopathy hs-cTnT : high sensitivity cardiac troponin T HTS : high throughput sequencing ICD : implantable cardioverter defibrillator ILR : implantable loop recorder INR : international normalized ratio IUD : intrauterine device LA : left atrium LAMP-2 : lysosome-associated membrane protein 2 LBBB : left bundle branch block LEOPARD : Lentigines, ECG abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, and sensory-neural Deafness LGE : late gadolinium enhancement LV : left ventricular LVAD : left ventricular assist device LVH : left ventricular hypertrophy LVOTO : left ventricular outlow tract obstruction MADIT-RIT : Multicenter Automatic Defibrillator Implantation Trial—Reduce Inappropriate Therapy MAPK : mitogen activated protein kinase MELAS : mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes MERFF : myoclonic epilepsy with ragged red fibres MRA : mineralocorticoid receptor antagonist MYBPC3 : myosin-binding protein C, cardiac-type MYH7 : myosin-7 (s-myosin heavy chain) MYL3 : myosin light chain 3 NOAC : new oral anticoagulants NSVT : non-sustained ventricular tachycardia NT-proBNP : N-terminal pro brain natriuretic peptide NYHA : New York Heart Association OAC : oral anticoagulants o.d. : omni die (every day) PC-CMR : phase contrast cardiac magnetic resonance PDE5 : phosphodiesterase type 5 PET : positron emission tomography PRKAG2 : gamma-2 sub-unit of the adenosine monophosphate-activated protein kinase RAAS : renin angiotensin aldosterone system RV : right ventricular SAM : systolic anterior motion SCD : sudden cardiac death SAA : septal alcohol ablation S-ICD™ : Subcutaneous lead implantable cardioverter defibrillator SPECT : single photon emission computed tomography SSFP : steady-state free precession SVT : supraventricular tachycardia TOE : transoesophageal echocardiography TNNI3 : troponin I, cardiac muscle TNNT2 : troponin T, cardiac muscle TPM1 : tropomyosin alpha-1 chain TTE : transthoracic echocardiography TTR : transthyretin VF : ventricular fibrillation VKA : vitamin K antagonist VT : ventricular tachycardia WHO : World Health Organization Guidelines summarize and evaluate all available evidence at the time of the writing process, on a particular issue with the aim of assisting health professionals in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk-benefit-ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help the health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. A great number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organisations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for management (including diagnosis, treatment, prevention and rehabilitation) of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic procedures was performed including assessment of the risk-benefit-ratio. Estimates of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular management options were weighed and graded according to predefined scales, as outlined in Tables 1 and 2 . The experts of …

Cardiovascular Magnetic Resonance Assessment of Human Myocarditis. A Comparison to Histology and Molecular Pathology

Background—Myocarditis can occasionally lead to sudden death and may progress to dilated cardiomyopathy in up to 10% of patients. Because the initial onset is difficult to recognize clinically and the diagnostic tools available are unsatisfactory, new strategies to diagnose myocarditis are needed. Methods and Results—Cardiovascular MR imaging (CMR) was performed in 32 patients who were diagnosed with myocarditis by clinical criteria. To determine whether CMR visualizes areas of active myocarditis, endomyocardial biopsy was taken from the region of contrast enhancement and submitted to histopathologic analysis. Follow-up was performed 3 month later. Contrast enhancement was present in 28 patients (88%) and was usually seen with one or several foci in the myocardium. Foci were most frequently located in the lateral free wall. In the 21 patients in whom biopsy was obtained from the region of contrast enhancement, histopathologic analysis revealed active myocarditis in 19 patients (parvovirus B19, n=12; human herpes virus type 6 [HHV 6], n=5). Conversely, in the remaining 11 patients, in whom biopsy could not be taken from the region of contrast enhancement, active myocarditis was found in one case only (HHV6). At follow-up, the area of contrast enhancement decreased from 9±11% to 3±4% of left ventricular mass as the left ventricular ejection fraction improved from 47±19% to 60±10%. Conclusions—Contrast enhancement is a frequent finding in the clinical setting of suspected myocarditis and is associated with active inflammation defined by histopathology. Myocarditis occurs predominantly in the lateral free wall. Contrast CMR is a valuable tool for the evaluation and monitoring of inflammatory heart disease.

Presentation, Patterns of Myocardial Damage, and Clinical Course of Viral Myocarditis

Background— Enteroviruses and adenoviruses have been considered the most common causes of viral myocarditis, but parvovirus B19 (PVB19) and human herpesvirus 6 (HHV6) are increasingly found in endomyocardial biopsy samples. Methods and Results— Consequently, our aim was to evaluate the prevalence and clinical presentation of cardiac PVB19 and/or HHV6 infection in a cohort of myocarditis patients and to follow its clinical course. In addition, we sought to demonstrate patterns of myocardial damage and to determine predictors for chronic heart failure. Our study design consisted of a cardiovascular magnetic resonance protocol as well as endomyocardial biopsies in the myocardial region affected as indicated by cardiovascular magnetic resonance. One hundred twenty-eight patients were enrolled by clinical criteria. In the group of myocarditis patients (n=87), PVB19 (n=49), HHV6 (n=16), and combined PVB19/HHV6 infections (n=15) were detected most frequently. The remaining patients were diagnosed with healing myocarditis (n=15) or did not have myocarditis (n=26). Patients with PVB19 presented in a manner similar to that of myocardial infarction; most had typical subepicardial late gadolinium enhancement in the lateral wall and recovered within months. Conversely, patients with HHV6 and especially with HHV6/PVB19 myocarditis presented with new onset of heart failure, had septal late gadolinium enhancement, and frequently progressed toward chronic heart failure. Conclusions— Our data indicate that PVB19 and HHV6 are the most important causes for viral myocarditis in Germany and that the clinical presentation is related to the type of virus. Furthermore, clinical presentation, type of virus, and pattern of myocardial damage are related to the clinical course.

Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy

OBJECTIVES We sought to ascertain whether myocardial scarring occurs in living unselected patients with hypertrophic cardiomyopathy (HCM). BACKGROUND Myocardial scarring is known to occur in select HCM patients, who were highly symptomatic prior to death or who died suddenly. The majority of HCM patients, however, are minimally symptomatic and have not suffered sudden death. METHODS Cine and gadolinium-enhanced magnetic resonance imaging was performed in 21 HCM patients who were predominantly asymptomatic. Gadolinium hyperenhancement was assumed to represent myocardial scar, and the extent of scar was compared to left ventricular (LV) morphology and function. RESULTS Scarring was present in 17 patients (81%). Scarring occurred only in hypertrophied regions (> or =10 mm), was patchy with multiple foci, and predominantly involved the middle third of the ventricular wall. All 17 patients had scarring at the junction of the interventricular septum and the right ventricular (RV) free wall. On a regional basis, the extent of scarring correlated positively with wall thickness (r = 0.36, p < 0.0001), and inversely with wall thickening (r = -0.21, p < 0.0001). On a per patient basis, the extent of scarring (mean, 8 +/- 9% of LV mass) was minimally related to maximum wall thickness (r = 0.40, p = 0.07) and LV mass (r = 0.33, p = 0.15), and correlated inversely with ejection fraction (r = -0.46, p = 0.04). CONCLUSIONS Myocardial scarring is common in asymptomatic or mildly symptomatic HCM patients who have not suffered sudden death. When present, scarring occurs in hypertrophied regions, is consistently localized to the junctions of the septum and RV free wall, and correlates positively with regional hypertrophy and inversely with regional contraction.

Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy.

OBJECTIVES We sought to establish the prognostic value of a comprehensive cardiovascular magnetic resonance (CMR) examination in risk stratification of hypertrophic cardiomyopathy (HCM) patients. BACKGROUND With annual mortality rates ranging between 1% and 5%, depending on patient selection, a small but significant number of HCM patients are at risk for an adverse event. Therefore, the identification of and prophylactic therapy (i.e., defibrillator placement) in patients with HCM who are at risk of dying are imperative. METHODS Two-hundred forty-three consecutive patients with HCM were prospectively enrolled. All patients underwent initial CMR, and 220 were available for clinical follow-up. The mean follow-up time was 1,090 days after CMR. End points were all-cause and cardiac mortality. RESULTS During follow-up 20 of the 220 patients died, and 2 patients survived sudden cardiac death due to adequate implantable cardioverter-defibrillator discharge. Most events (n = 16) occurred for cardiac reasons; the remaining 6 events were related to cancer and accidents. Our data indicate that the presence of scar visualized by CMR yields an odds ratio of 5.47 for all-cause mortality and of 8.01 for cardiac mortality. This might be superior to classic clinical risk factors, because in our dataset the presence of 2 risk factors yields an odds ratio of 3.86 for all-cause and of 2.20 for cardiac mortality, respectively. Multivariable analysis also revealed the presence of late gadolinium enhancement as a good independent predictor of death in HCM patients. CONCLUSIONS Among our population of largely low or asymptomatic HCM patients, the presence of scar indicated by CMR is a good independent predictor of all-cause and cardiac mortality.

Reproducibility of Chronic Infarct Size Measurement by Contrast-Enhanced Magnetic Resonance Imaging

Background—The reproducibility of contrast-enhanced MRI has not been established. We compared MRI reproducibility for infarct size determination with that of 99mTc-sestamibi (MIBI) single photon emission computed tomography (SPECT). Methods and Results—Patients with chronic myocardial infarction defined by enzymes (peak creatine kinase-MB 173±119 U/L) were scanned twice by MRI (MRI I and MRI II, n=20) and twice by SPECT (SPECT I and SPECT II, n=15) on the same day. The MRI contrast agent was injected during MRI I but not MRI II to test the effect of imaging time after contrast. Resting Tc-MIBI SPECT images were acquired and infarct size was determined with commercial software. Infarct size in patients scanned by MRI and SPECT was 14±6% of left ventricular mass (%LV) by MRI (range 4%LV to 27%LV) and 14±7%LV by SPECT (range 4%LV to 26%LV). MRI I and II scans were performed 10±2 and 27±3 minutes after contrast, respectively. For MRI, the difference in infarct size between scans I and II (bias) was −0.1%LV, and the coefficient of repeatability was ±2.4%LV. For SPECT, bias was −1.3%LV, and the coefficient of repeatability was ±4.0%LV. Within individual patients, no systematic differences in infarct size were detected when the 2 MRI scans were compared, the 2 SPECT scans were compared, or MRI was compared to SPECT. Conclusion—The size of healed infarcts measured by contrast-enhanced MRI does not change between 10 and 30 minutes after contrast. The clinical reproducibility of contrast-enhanced MRI for infarct size determination compares favorably with that of routine clinical SPECT.

Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: noninvasive imaging compared to endomyocardial biopsy.

OBJECTIVES We sought to evaluate the diagnostic performance of cardiovascular magnetic resonance imaging (CMRI) for detection of cardiac amyloidosis compared with endomyocardial biopsy (EMB) in a clinical routine setting. BACKGROUND For the clinical workup of heart failure with restrictive filling, pattern cardiac amyloidosis is an important differential diagnosis that is difficult to verify with current noninvasive techniques, especially in the presence of myocardial hypertrophy. METHODS A total of 33 consecutive patients underwent both CMRI and EMB for workup of heart failure with restrictive filling pattern in combination with myocardial hypertrophy (n = 24) and/or clinical conditions often associated with cardiac amyloidosis (n = 18). RESULTS Cardiac amyloidosis was detected by EMB in 15 of the 33 patients. In patients with biopsy-proven cardiac amyloidosis, CMRI revealed a distinct pattern of late gadolinium enhancement, which was distributed over the entire subendocardial circumference, extending in various degrees into the neighboring myocardium. This pattern was found in 12 of the 15 patients diagnosed with cardiac amyloidosis by EMB, compared with only 1 individual in the group of 18 patients diagnosed with other myocardial diseases. Consequently, using this pattern as a diagnostic criterion, the sensitivity of CMRI for diagnosing cardiac amyloidosis was 80%, yielding a specificity of 94%. The positive predictive value was 92%, and the negative predictive value was 85%. CONCLUSIONS In patients with biopsy-proven cardiac amyloidosis, late gadolinium enhancement frequently occurs in a peculiar pattern. On the basis of the gold standard, EMB, noninvasive CMRI can be used to diagnose or rule out cardiac amyloidosis with good sensitivity and excellent specificity in a clinical routine setting.

Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis Predictors of Mortality and Incomplete Recovery

OBJECTIVES This study sought to evaluate the long-term mortality in patients with viral myocarditis, and to establish the prognostic value of various clinical, functional, and cardiovascular magnetic resonance (CMR) parameters. BACKGROUND Long-term mortality of viral myocarditis, as well as potential risk factors for poor clinical outcome, are widely unknown. METHODS A total of 222 consecutive patients with biopsy-proven viral myocarditis and CMR were enrolled. A total of 203 patients were available for clinical follow-up, and 77 patients underwent additional follow-up CMR. The median follow-up was 4.7 years. Primary endpoints were all-cause mortality and cardiac mortality. RESULTS We found a relevant long-term mortality in myocarditis patients (19.2% all cause, 15% cardiac, and 9.9% sudden cardiac death [SCD]). The presence of late gadolinium enhancement (LGE) yields a hazard ratio of 8.4 for all-cause mortality and 12.8 for cardiac mortality, independent of clinical symptoms. This is superior to parameters like left ventricular (LV) ejection fraction, LV end-diastolic volume, or New York Heart Association (NYHA) functional class, yielding hazard ratios between 1.0 and 3.2 for all-cause mortality and between 1.0 and 2.2 for cardiac mortality. No patient without LGE experienced SCD, even if the LV was enlarged and impaired. When focusing on the subgroup undergoing follow-up CMR, we found an initial NYHA functional class >I as the best independent predictor for incomplete recovery (p = 0.03). CONCLUSIONS Among our population with a wide range of clinical symptoms, biopsy-proven viral myocarditis is associated with a long-term mortality of up to 19.2% in 4.7 years. In addition, the presence of LGE is the best independent predictor of all-cause mortality and of cardiac mortality. Furthermore, initial presentation with heart failure may be a good predictor of incomplete long-term recovery.