Michael Kindermann

Predictors of Outcome in Patients With Suspected Myocarditis

Background— The objective of this study was to identify the prognostic indicators in patients with suspected myocarditis who underwent endomyocardial biopsy. Methods and Results— Between 1994 and 2007, 181 consecutive patients (age, 42±15 years) with clinically suspected viral myocarditis were enrolled and followed up for a mean of 59±42 months. Endomyocardial biopsies were studied for inflammation with histological (Dallas) and immunohistological criteria. Virus genome was detected by polymerase chain reaction. The primary end point was time to cardiac death or heart transplantation. In 38% of the patients (n=69), the Dallas criteria were positive. Immunohistological signs of inflammation were shown in 50% (n=91). Genomes of cardiotropic virus species were detected in 79 patients (44%). During follow-up, 22% of the patients (n=40) reached the primary end point. Three independent predictors were identified for the primary end point, namely New York Heart Association class III or IV at entry (hazard ratio, 3.20; 95% confidence interval, 1.36 to 7.57; P=0.008), immunohistological evidence of inflammatory infiltrates in the myocardium (hazard ratio, 3.46; 95% confidence interval, 1.39 to 8.62; P=0.008), and β-blocker therapy (hazard ratio, 0.43; 95% confidence interval, 0.21 to 0.91; P=0.027). Ejection fraction, left ventricular end-diastolic pressure, and left ventricular end-diastolic dimension index were predictive only in univariate, not in multivariate, analysis. Neither the Dallas criteria nor the detection of viral genome was a predictor of outcome. Conclusions— For patients with suspected myocarditis, advanced New York Heart Association functional class, immunohistological signs of inflammation, and lack of β-blocker therapy, but not histology (positive Dallas criteria) or viral genome detection, are related to poor outcome.

Comparative Evaluation of Left and Right Ventricular Endomyocardial Biopsy Differences in Complication Rate and Diagnostic Performance

Background— Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin. Methods and Results— In this 2-center study, 755 patients with clinically suspected myocarditis (n=481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (n=274) underwent either selective LV-EMB (n=265; 35.1%), selective RV-EMB (n=133; 17.6%), or biventricular EMB (n=357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardial effusion that occurred after biventricular EMB, the minor complication rate for LV-EMB varied between 0.64% to 2.89% and for RV-EMB, between 2.24% and 5.10%. Diagnostic EMB results were achieved significantly more often in those patients who underwent biventricular EMBs (79.3%) compared to those who underwent either selective LV-EMB or selective RV-EMB (67.3%; P<0.001). In patients with biventricular EMB, myocarditis was diagnosed in LV-EMB samples in 18.7% and in RV-EMB samples in 7.9% (P=0.002), and it was diagnosed in both ventricles in 73.4%. There were no differences in the number of positive LV-EMB, RV-EMB, or LV- and RV-EMB findings when related to the site of cardiovascular magnetic resonance–based late gadolinium enhancement. Conclusions— Both LV-EMB and RV-EMB are safe procedures if performed by experienced interventionalists. The diagnostic yield of EMB may be optimized when samples from both ventricles are available. Preferential biopsy in regions showing late gadolinium enhancement on cardiovascular magnetic resonance does not increase the number of positive diagnoses of myocarditis.

Influence of right ventricular stimulation site on left ventricular function in atrial synchronous ventricular pacing

OBJECTIVES The study investigates the correlation between left ventricular function and QRS duration obtained by alternate right ventricular pacing sites. BACKGROUND 1. Right ventricular apical pacing is associated with alterations of left ventricular contraction sequence. 2. A stimulation producing narrow QRS complexes is supposed to provide for better left ventricular contraction patterns. METHODS Fourteen patients with third degree AV block received one ventricular pacing lead in apical position. The alternate lead was attached to that site on the septum that produced the smallest QRS complex as measured from the earliest to the last deflection in any of the orthogonal Frank leads (xyz). During atrial synchronous ventricular pacing, the AV delay was optimized individually and for each stimulation site using mitral valve doppler or impedance cardiography. By radionuclide ventriculography, the phase distribution histogram of left ventricular contraction was evaluated as area under the curve (AuC); systolic function was determined as ejection fraction (EF) and as absolute ejected counts (EC) in random order. The difference (delta) in QRS duration between apical and septal stimulation (deltaxyz) was correlated with the difference in phase distribution (deltaAuC) and ejection parameters (deltaEF, deltaEC). RESULTS QRS duration was shorter with septal than with apical pacing in 9 out of 14 patients (64%); it was longer in 4 (29%), and no difference was seen in 1 patient. There was a significant positive correlation between the change in QRS duration (deltaxvz) and phase distribution (deltaAuC: r = 0.66393, p = 0.010) and a significant negative correlation to systolic function (deltaEF: r = 0.70931, p = 0.004; deltaEC: r = 0.74368, p = 0.002). CONCLUSIONS In atrial synchronous right ventricular pacing, if the AV delay is adapted individually, decreased QRS duration obtained by alternate pacing sites is significantly correlated with homogenization of left ventricular contraction and with increased systolic function in acute tests.

Cardiorespiratory Response to Exercise After Renal Sympathetic Denervation in Patients With Resistant Hypertension

OBJECTIVES This study sought to investigate the effects of interventional renal sympathetic denervation (RD) on cardiorespiratory response to exercise. BACKGROUND RD reduces blood pressure at rest in patients with resistant hypertension. METHODS We enrolled 46 patients with therapy-resistant hypertension as extended investigation of the Symplicity HTN-2 (Renal Denervation With Uncontrolled Hypertension) trial. Thirty-seven patients underwent bilateral RD and 9 patients were assigned to the control group. Cardiopulmonary exercise tests were performed at baseline and 3-month follow-up. RESULTS In the RD group, compared with baseline examination, blood pressure at rest and at maximum exercise after 3 months was significantly reduced by 31 ± 13/9 ± 13 mm Hg (p < 0.0001) and by 21 ± 20/5 ± 14 mm Hg (p < 0.0001), respectively. Achieved work rate increased by 5 ± 13 W (p = 0.029) whereas peak oxygen uptake remained unchanged. Blood pressure 2 min after exercise was significantly reduced by 29 ± 17/8 ± 15 mm Hg (p < 0.001 for systolic blood pressure; p = 0.002 for diastolic blood pressure). Heart rate at rest decreased after RD (4 ± 11 beats/min; p = 0.028), whereas maximum heart rate and heart rate increase during exercise were not different. Heart rate recovery improved significantly by 4 ± 7 beats/min after renal denervation (p = 0.009). In the control group, there were no significant changes in blood pressure, heart rate, maximum work rate, or ventilatory parameters after 3 months. CONCLUSIONS RD reduces blood pressure during exercise without compromising chronotropic competence in patients with resistant hypertension. Heart rate at rest decreased and heart rate recovery improved after the procedure. (Renal Denervation With Uncontrolled Hypertension; [Symplicity HTN-2]; NCT00888433).

Virus serology in patients with suspected myocarditis: utility or futility?

AIMS Serological analyses of viral infection in suspected myocarditis are still widely used, although convincing evidence for their value is lacking. We determined prospectively the diagnostic value of virus serology in comparison with endomyocardial biopsy (EMB) including viral genome detection and immunohistochemistry in patients with clinically suspected myocarditis. METHODS AND RESULTS Virus serology and state-of-the-art evaluation of EMB were performed in 124 patients (age 40 ± 15 years) with suspected myocarditis. Endomyocardial biopsy was studied for inflammation with histological and immunohistological criteria. The viral genome was detected in the myocardium by polymerase chain reaction. Acute viral infection with enterovirus, adenovirus, parvovirus B19, cytomegalovirus, human herpesvirus, and Epstein-Barr virus was diagnosed by IgM or IgA in the initial sample or IgG seroconversion in the follow-up sample. Immunohistological signs of inflammation were present in 54 patients. The viral genome was detected in the myocardium of 58 patients (47%). In 20 patients (16%), acute viral infection was diagnosed by serology. Only in 5 out of 124 patients (4%), there was serological evidence of an infection with the same virus that was detected by EMB. Sensitivity and specificity of virus serology were 9 and 77%, respectively. The positive predictive value was 25% and the negative predictive value was 49%. The lack of correlation between serology and EMB remained also for patients with biopsy-proven myocarditis and patients with time from initial symptoms to EMB procedure of ≤1 month. CONCLUSIONS For patients with suspected myocarditis, virus serology has no relevance for the diagnosis of myocardial infection. Endomyocardial biopsy remains the gold standard in the diagnostic of viral myocarditis.

RING+STRING Successful Repair Technique for Ischemic Mitral Regurgitation With Severe Leaflet Tethering

Background— Residual/recurrent mitral valve regurgitation is observed in 30% after undersized ring annuloplasty (RING) for ischemic mitral regurgitation (IMR). RING addresses primarily annular dilatation but does not correct severe leaflet tethering attributable to papillary muscle (PM) displacement. We proposed adjunctive PM repositioning under transesophageal echocardiography (TEE) guidance in the loaded beating heart using a transventricular suture (STRING). Methods and Results— Patients with tenting height ≥10 mm were identified as high-risk patients for repair failure. In these patients (n=30, age 68±11 years, ejection fraction 37±14%), RING (partial, median 29 mm) was combined with the adjunctive STRING-technique. A Teflon-pledgeted 3-0-polytetrafluoroethylene-suture was anchored in the posterior PM via horizontal aortotomy, exteriorized through the aorto-mitral continuity, and tied in the loaded beating heart under TEE guidance. Tenting height (14±2 mm versus 6±1 mm, P<0.001) and tenting area (3.9±0.9 cm2 versus 1.0±0.2 cm2, P<0.001) decreased. The distance between pPM and aorto-mitral continuity decreased (44±4 mm versus 37±3 mm, P<0.001). Survival at 2 years was similar compared with a historical matched control-group (89% versus 73%, P=0.13), whereas freedom from MR>II was higher in the RING+STRING-group (94% versus 71%, P=0.01). End-diastolic (61.7±7.2 mm versus 54.8±9.2 mm, P<0.001) and end-systolic (48.5±8.5 mm versus 42.7±7.8 mm, P=0.002) ventricular diameters decreased in the RING+STRING-group but persisted in the control-group (60.4±7.8 mm versus 58.9±7.5 mm, P=0.38; 47.8±9.6 mm versus 48.3±9.5 mm, P=0.52). During follow-up (median 26 months) only 1 patient of the study-group required reoperation for degenerative MR, while 2 control-group patients underwent reoperation for recurrent functional MR. Conclusions— Our novel approach for IMR attenuates high risk of repair failure in patients with severe leaflet tethering and results in reverse remodeling.

Prognostic electrocardiographic parameters in patients with suspected myocarditis

The objective of this study was to investigate the prognostic value of electrocardiographic (ECG) parameters for outcome in patients acutely admitted with myocarditis without previous heart failure who underwent endomyocardial biopsy.

Cognitive function in patients with decompensated heart failure: the Cognitive Impairment in Heart Failure (CogImpair‐HF) study

The objective of this study was to examine cognitive and psychological processes systematically in patients with decompensated chronic heart failure (CHF) and to document changes in cognitive function after compensation. Executive functions, episodic memory, and attention are impaired in patients with stable CHF, influencing health behaviour and disease management. Cognitive function and psychological co‐morbidities are associated with hospitalization, disability, and mortality.

The Influence of Right Atrial Septal Pacing on the Interatrial Contraction Sequence

Right atrial septal pacing yields shorter interatrial conduction delays than conventional right atrial pacing at the free wall or the right atrial appendage. However, the hemodynamic effects of right atrial septal pacing are less well known. This study measured the delay between right and left atrial contractions during right atrial septal pacing (n = 21), conventional right atrial pacing (n = 32) and atrial multisite pacing (n = 6) by pulse Doppler echocardiography of transtricuspidal and transmitral blood flow. The effects of right atrial septal pacing (n = 14) versus conventional right atrial pacing (n = 22) on the optimal AV delay during dual chamber pacing was examined in patients with high degree atrioventricular (AV) block. Compared to sinus rhythm, conventional right atrial pacing increased P wave duration from 119 ± 21 ms to 137 ± 24 ms (P < 0.001), whereas both right atrial septal pacing (119 ± 10 ms before, 106 ± 13 ms during pacing, P = 0.002) and atrial multisite pacing (123 ± 20 ms before, 112 ± 11 ms during pacing, P = 0.5) shortened P wave duration. Atrial pacing caused a significant (P < 0.002) prolongation of atrial conduction delays from 24 ± 21 ms to 41 ± 26 ms during conventional right atrial pacing, and reversed the right‐to‐left into a left‐to‐right contraction sequence in 20 of 21 patients during right atrial septal pacing (atrial conduction delay during sinus rhythm: 34 ± 23 ms vs 37 ± 26 ms during atrial pacing, P < 0.0001). Atrial multisite pacing caused a nonsignificant shortening of the usual right‐to‐left contraction delay from 22 ± 34 ms to 11 ± 18 ms. The optimal left heart AV delay during AV sequential pacing was significantly (P = 0.002) shorter during right atrial septal pacing (108 ± 38 ms) than during conventional right atrial pacing (152 ± 33 ms). During conventional right atrial pacing the optimal right heart AV delay was significantly (P = 0.029) shorter than the optimal left heart AV delay. The opposite relation was observed for right atrial septal pacing (P = 0.033). Conclusions: Interatrial septal pacing does not synchronize right and left atrial contractions. It reverses the atrial mechanical timing from a right‐to‐left to a left‐to‐right contraction sequence, and requires the setting of shorter AV delays during dual chamber pacing if based on the optimization of left heart timing. Interatrial septal pacing is a technique which allows pacing of the left atrium from a right atrial site, rather than a single site approach to biatrial pacing.

Pulmonary hypertension due to left heart disease: Updated Recommendations of the Cologne Consensus Conference 2011

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH including PH owing to left heart disease. The guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors) have not been sufficiently investigated in other forms of PH. However, despite the lack of respective efficacy data an uncritical use of targeted PAH drugs in patients with PH associated with left heart disease is currently observed at an increasing rate. This development is a matter of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary describes in detail the results and recommendations of the working group which were last updated in October 2011.