Pulmonary embolism versus pulmonary vasculitis in Hughes-Stovin syndrome: Characteristic computed tomography pulmonary angiographic findings and diagnostic and therapeutic implications. HSS International Study Group.

BACKGROUND AND AIM: Hughes-Stovin syndrome (HSS) is a rare systemic vasculitis with widespread venous/arterial thrombosis and pulmonary vasculitis. Distinguishing between pulmonary embolism (PE) and in-situ thrombosis in the early stages of HSS is challenging. The aim of the study is to compare clinical, laboratory, and computed tomography pulmonary angiography (CTPA) characteristics in patients diagnosed with PE versus those with HSS. METHODS: This retrospective study included 40 HSS patients with complete CTPA studies available, previously published by the HSS study group, and 50 patients diagnosed with PE from a single center. Demographics, clinical and laboratory findings, vascular thrombotic events, were compared between both groups. The CTPA findings were reviewed, with emphasis on the distribution, adherence to the mural wall, pulmonary infarction, ground glass opacification, and intra-alveolar hemorrhage. Pulmonary artery aneurysms (PAAs) in HSS were assessed and classified. RESULTS: The mean age of HSS patients was 35 ± 12.3 years, in PE 58.4 ± 17 (p < 0.0001). Among PE 39(78 %) had co-morbidities, among HSS none. In contrast to PE, in HSS both major venous and arterial thrombotic events are seen.. Various patterns of PAAs were observed in the HSS group, which were entirely absent in PE. Parenchymal hemorrhage was also more frequent in HSS compared to PE (P < 0.001). CONCLUSION: Major vascular thrombosis with arterial aneurysms formation are characteristic of HSS. PE typically appear loosely-adherent and mobile whereas "in-situ thrombosis" seen in HSS is tightly-adherent to the mural wall. Mural wall enhancement and PAAs are distinctive pulmonary findings in HSS. The latter findings have significant therapeutic ramifications.

Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS.

BACKGROUND: Glycyrrhizin, an active component of liquorice root extract, exhibits antiviral and immunomodulatory properties by direct inhibition of the pro-inflammatory alarmin HMGB1 (High-mobility group box 1). OBJECTIVE: The aim of this study was to explore the role of liquorice intake on the viral entry receptor ACE2 (angiotensin-converting enzyme 2) and the immunoregulatory HMGB1 in healthy individuals and to explore HMGB1 expression in coronavirus disease 2019 (COVID-19) or non-COVID-19 in ARDS (acute respiratory distress syndrome patients). MATERIAL AND METHODS: This study enrolled 43 individuals, including hospitalised patients with i) acute respiratory distress syndrome (ARDS) due to COVID-19 (n = 7) or other underlying causes (n = 12), ii) mild COVID-19 (n = 4) and iii) healthy volunteers (n = 20). Healthy individuals took 50 g of liquorice (containing 3% liquorice root extract) daily for 7 days, while blood samples were collected at baseline and on day 3 and 7. Changes in ACE2 and HMGB1 levels were determined by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Additionally, HMGB1 levels were measured in hospitalised COVID-19 patients with mild disease or COVID-19 associated acute respiratory distress syndrome (ARDS) and compared with a non-COVID-19-ARDS group. RESULTS: Liquorice intake significantly reduced after 7 days both cellular membranous ACE2 expression (-51% compared to baseline levels, p = 0.008) and plasma HMGB1 levels (-17% compared to baseline levels, p<0.001) in healthy individuals. Half of the individuals had a reduction in ACE2 levels of at least 30%. HMGB1 levels in patients with mild COVID-19 and ARDS patients with and without COVID-19 were significantly higher compared with those of healthy individuals (+317%, p = 0.002), but they were not different between COVID-19 and non-COVID-19 ARDS. CONCLUSIONS: Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.

Pulmonary vasculitis in Hughes-Stovin syndrome (HSS): a reference atlas and computed tomography pulmonary angiography guide-a report by the HSS International Study Group.

INTRODUCTION: Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by widespread venous/arterial thrombosis and pulmonary artery aneurysms (PAAs), which is associated with serious morbidity and mortality. All fatalities reported in HSS resulted from unpredictable fatal suffocating hemoptysis. Therefore, it is necessary to recognize pulmonary complications at an early stage of the disease. OBJECTIVES: The aims of this study are to develop a reference atlas of images depicting the characteristic features of HSS by computed tomography pulmonary angiography (CTPA). To make a guide for physicians by developing a classification of PAAs according to the severity and risk of complications associated with each distinct lesion type. METHODS: The Members of the HSS International Study Group (HSSISG) collected 42 cases, with high-quality CTPA images in one radiology station and made reconstructions from the source images. These detailed CTPA studies were reviewed for final image selection and approved by HSSISG board members. We classified these findings according to the clinical course of the patients. RESULTS: This atlas describes the CTPA images that best define the wide spectrum of pulmonary vasculitis observed in HSS. Pulmonary aneurysms were classified into six radiographic patterns: from true stable PAA with adherent in-situ thrombosis to unstable leaking PAA, BAA and/or PAP with loss of aneurysmal wall definition (most prone to rupture), also CTPA images demonstrating right ventricular strain and intracardiac thrombosis. CONCLUSION: The HSSISG reference atlas is a guide for physicians regarding the CTPA radiological findings, essential for early diagnosis and management of HSS-related pulmonary vasculitis. Key Points • The Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by extensive vascular thrombosis and pulmonary artery aneurysms (PAAs) that can lead to significant morbidity and mortality. • All fatalities reported in HSS were related to unpredictable massive hemoptysis; therefore, it is critical to recognize pulmonary complications at an early stage of the disease. • The HSS International Study Group reference atlas  classifies pulmonary vasculitis in HSS at 6 different stages of the disease process and defines the different radiological patterns of pulmonary vasculitis notably pulmonary artery aneurysms, as detected by computed tomography pulmonary angiography (CTPA). • The main aim of the classification is to make a guide for physicians about this rare syndrome. Such a scheme has never been reached before since the first description of the syndrome by Hughes and Stovin since 1959. This classification will form the basis for future recommendations regarding diagnosis and treatment of this syndrome.

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19.

BACKGROUND: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. PATIENTS AND METHODS: Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. RESULTS: The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). DISCUSSION: Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

A critical analysis of 57 cases of Hughes-Stovin syndrome (HSS). A report by the HSS International Study Group (HSSISG).

BACKGROUND: Hughes-Stovin syndrome (HSS) is a systemic disease characterized by widespread vascular thrombosis and pulmonary vasculitis with serious morbidity and mortality. The HSS International Study Group is a multidisciplinary taskforce aiming to study HSS, in order to generate consensus recommendations regarding diagnosis and treatment. METHODS: We included 57 published cases of HSS (43 males) and collected data regarding: clinical presentation, associated complications, hemoptysis severity, laboratory and computed tomography pulmonary angiography (CTPA) findings, treatment modalities and cause of death. RESULTS: At initial presentation, DVT was observed in 29(33.3 %), thrombophlebitis in 3(5.3%), hemoptysis in 24(42.1%), and diplopia and seizures in 1 patient each. During the course of disease, DVT occurred in 48(84.2%) patients, and superficial thrombophlebitis was observed in 29(50.9%). Hemoptysis occurred in 53(93.0%) patients and was fatal in 12(21.1%). Pulmonary artery (PA) aneurysms (PAAs) were bilateral in 53(93%) patients. PAA were located within the main PA in 11(19.3%), lobar in 50(87.7%), interlobar in 13(22.8%) and segmental in 42(73.7%). Fatal outcomes were more common in patients with inferior vena cava thrombosis (p = 0.039) and ruptured PAAs (p < 0.001). Death was less common in patients treated with corticosteroids (p < 0.001), cyclophosphamide (p < 0.008), azathioprine (p < 0.008), combined immune modulators (p < 0.001). No patients had uveitis; 6(10.5%) had genital ulcers and 11(19.3%) had oral ulcers. CONCLUSIONS: HSS may lead to serious morbidity and mortality if left untreated. PAAs, adherent in-situ thrombosis and aneurysmal wall enhancement are characteristic CTPA signs of HSS pulmonary vasculitis. Combined immune modulators contribute to favorable outcomes.

Fast spontaneous recovery from acute necrotizing eosinophilic myopericarditis without need for immunosuppressive therapy: a case report of a 27-year-old male.

BACKGROUND: Eosinophilic myocarditis (EM) is rare but accounts for 12-22% of histologically proven acute myocarditis cases. Acute necrotizing EM is considered an aggressive, life-threatening disease which is usually treated by high-dose corticosteroid therapy. CASE SUMMARY: We report the case of a 27-year-old man with acute severe pericarditic chest pain, moderately reduced left ventricular (LV) ejection fraction, and a small pericardial effusion. Troponin I level was highly elevated in the absence of coronary artery disease, leading to the diagnosis of acute myopericarditis. In the absence of blood eosinophilia and despite a negative cardiac magnetic resonance study, LV endomyocardial biopsy revealed an acute necrotizing EM. With conventional antiphlogistic and heart failure therapy, the patient became symptom-free and inflammatory and cardiac necrosis markers as well as LV ejection fraction normalized within days. Thus, in the absence of a systemic hypereosinophilic disorder, there was no need for steroid therapy. Long-term follow-up over 12 months showed sustained normalization of cardiac structure and function. DISCUSSION: Acute necrotizing eosinophilic myopericarditis is not always a dreadful cardiac disease. There are idiopathic cases which may quickly resolve without immunosuppression. There seems to be a publication bias towards critical cases.

Percutaneous closure of an iatrogenic aorto-right atrial fistula of the sinus of Valsalva through total arm approach: a case report.

BACKGROUND: Creation of an iatrogenic aorto-right atrial fistula is a rare but clinically relevant complication of cardiac surgery. Transfemoral percutaneous closure is an attractive alternative to surgical repair, but there are no reports about transcatheter repair using a complete arm access. CASE SUMMARY: We present the case of a 44-year-old woman with heart failure (NewYork Heart Association Class III) due to a longstanding iatrogenic fistula from the non-coronary aortic cusp to the right atrium (RA) with aorta to RA shunting and severe tricuspid regurgitation (TR) caused by mitral valve replacement 15 years ago. The patient was successfully treated by percutaneous closure with an Amplatzer Vascular Plug II using complete brachial access. Following the procedure right heart chambers and TR decreased and symptoms resolved. DISCUSSION: To the best of our knowledge this is the first report of percutaneous repair of an aorto-right atrial fistula using total arm accesses (radial artery and basilic vein). In appropriately selected patients, this approach is an attractive alternative to femoral access.

Treatment of femoro-popliteal lesions with scoring and drug-coated balloon angioplasty: 12-month results of the DCB-Trak registry.

PURPOSE: Debulking strategies prior to drug-coated balloon (DCB) angioplasty were suggested to improve clinical results in femoro-popliteal lesions. Currently, there are no data regarding plaque modification with a scoring balloon with subsequent DCB-angioplasty. Recently published 6-month results of the DCB-Trak registry in patients treated with scoring-balloon angioplasty and DCB-angioplasty were promising without any safety concerns. Herein, we report the 12-month follow-up data. METHODS: In a single center registry, 29 consecutive patients with 32 femoro-popliteal lesions were treated with a scoring-balloon (VascuTrak®) and a DCB subsequently. The primary endpoint was the clinically driven target lesion revascularization (TLR). Secondary endpoints were clinically driven target vessel revascularization (TVR), binary restenosis (peak systolic velocity ratio > 2.4), change in Rutherford classification and ankle-brachial-index (ABI). Safety endpoints were major cardiovascular events (cardiovascular death, myocardial infarction, stroke, death) and need for amputation. RESULTS: The procedure was successful in 29 lesions. There were no clinically driven TLRs after 12 months. Two patients required clinically driven TVR and one patient had a binary restenosis. ABI significantly increased after the procedure (0.87±0.24 to 1.04±0.18, P < 0.01) without a relevant change after 6 months (1.01±0.15, P < 0.05) or 12 months (1.01±0.20, P < 0.05). Rutherford classification improved in more than 90% of patients after 6 and 12 months. There was one major cardiovascular event at 6-month follow-up, but no amputations at 6- or 12-month follow-up. CONCLUSION: Vessel preparation with a scoring-balloon and subsequent DCB-angioplasty was safe and effective in patients with femoro-popliteal lesions. Further multicenter trials have to validate these results.

Diagnostic and prognostic validity of different biomarkers in patients with suspected myocarditis.

BACKGROUND: Myocarditis might be associated with increased markers of myocardial injury. However, data on novel biomarkers, such as high-sensitive Troponin T (hs-TnT) or Copeptin, are lacking. This study aimed to determine the diagnostic and prognostic utility of biomarkers in patients with suspected myocarditis. METHODS: Seventy patients with clinically suspected myocarditis (age 43.4 ± 14 years, 76 % male, ejection fraction 36.9 ± 17.8) underwent endomyocardial biopsy (EMB) and were followed for 7.5 (2-21) months. At the time of EMB, blood samples to evaluate concentrations of hs-TnT, Copeptin, NT-proBNP and mid-regional pro-adrenomedullin (MR-proADM) were collected. RESULTS: According to EMB, 6 patients were diagnosed with acute myocarditis (AM) and 36 patients with chronic myocarditis (CM). In 28 patients, EMB revealed no myocardial inflammation (NM). Acute myocarditis was associated with the highest concentrations of hs-TnT compared to other groups (AM 262.9 pg/ml (61.4-884.2); CM 20.4 pg/ml (15.6-20.4); NM 19.5 pg/ml (13.8-50.7); p < 0.0001). No significant differences existed in the Copeptin, NT-proBNP, and MR-proADM concentrations between the groups. The concentration of hs-TnT was significantly higher in myocarditis when myocardial viral genome was detected (37.4 pg/ml (21.9-163.6) vs. 20 pg/ml (14-44.4); p = 0.042). During follow-up, only NT-proBNP in the highest quartile (>4,225 ng/ml) was predictive for cardiac death or heart transplantation (hazard ratio 9.2; 95% confidence interval 1.7-50; p = 0.011). CONCLUSIONS: Biopsy-proven acute and viral myocarditis is associated with elevated concentrations of hs-TnT. Elevated hs-TnT is highly suggestive of acute myocarditis, if other causes of increased myocardial necrosis markers such as myocardial infarction have been systematically excluded.

Improvements in left ventricular hypertrophy and diastolic function following renal denervation: effects beyond blood pressure and heart rate reduction.

OBJECTIVES: This study sought to investigate the interaction between blood pressure (BP) and heart rate (HR) reduction and changes in left ventricular (LV) structure and function following renal sympathetic denervation (RDN). BACKGROUND: Hypertension results in structural and functional cardiac changes. RDN reduces BP, HR, and LV mass and improves diastolic dysfunction. METHODS: We evaluated LV size, mass, and function before and 6 months after RDN in 66 patients with resistant hypertension and analyzed results in relation to systolic BP (SBP) and HR. RESULTS: SBP decreased by 11 ± 3 mm Hg in the first, 18 ± 5 mm Hg in the second, and 36 ± 7 mm Hg in the third tertile of SBP at baseline (p < 0.001). HR decreased by 13 ± 4 beats/min, 8 ± 3 beats/min, and 11 ± 6 beats/min in tertiles of SBP (p for interaction between tertiles = 0.314). In all SBP tertiles, LV mass index (LVMI) decreased similarly (LVMI -6.3 ± 2.2 g/m(2.7), -8.3 ± 2.1 g/m(2.7), and -9.6 ± 1.9 g/m(2.7); p for interaction = 0.639). LVMI decreased unrelated to HR at baseline (p for interaction = 0.471). The diastolic parameters E-wave deceleration time, isovolumetric relaxation time, and E'-wave velocity improved similarly in all tertiles of SBP and HR. Changes in LV mass and function were also unrelated to reduction in SBP or HR. Vascular compliance improved dependently on BP but independently of HR reduction. CONCLUSIONS: In patients with resistant hypertension, LV hypertrophy and diastolic function improved 6 months after RDN, without significant relation to SBP and HR. These findings suggest a direct effect of altered sympathetic activity in addition to unloading on cardiac hypertrophy and function.

Aortic valve function after bicuspidization of the unicuspid aortic valve.

BACKGROUND: Unicuspid aortic valve (UAV) anatomy leads to dysfunction of the valve in young individuals. We introduced a reconstructive technique of bicuspidizing the UAV. Initially we copied the typical asymmetry of a normal bicuspid aortic valve (BAV) (I), later we created a symmetric BAV (II). This study compared the hemodynamic function of the two designs of a bicuspidized UAV. METHODS: Aortic valve function was studied at rest and during exercise in 28 patients after repair of UAV (group I, n = 8; group II, n = 20). There were no differences among the groups I and II with respect to gender, age, body size, or weight. All patients were in New York Heart Association class I. Six healthy adults served as control individuals. All patients were studied with transthoracic echocardiography between 4 and 65 months postoperatively. Systolic gradients were assessed by continuous wave Doppler while patients were at rest and exercising on a bicycle ergometer. RESULTS: Aortic regurgitation was grade I or less in all patients. Resting gradients were significantly elevated in group I compared with group II and control individuals (group I, peak 33.8 ± 7.8 mm Hg; mean 19.1 ± 5.4 mm Hg; group II, peak 15.8 ± 5.4, mean 8.2 ± 2.8 mm Hg; control individuals, peak 6.0 ± 1.6, mean 3.2 ± 0.8 mm Hg; p < 0.001). At 100 W peak gradients were highest in group I (group I, 62.7 ± 16.7 mm Hg; group II, 28.1 ± 7.6 mm Hg; control individuals, 15.4 ± 4.6 mm Hg; p < 0.001). CONCLUSIONS: Converting a UAV into a symmetric bicuspid design results in adequate valve competence. A symmetric repair design leads to improved systolic aortic valve function at rest and during exercise.

Blood pressure and heart rate predict outcome in patients acutely admitted with suspected myocarditis without previous heart failure.

OBJECTIVE: The study investigated the prognostic impact of blood pressure and heart rate in patients acutely admitted with suspected myocarditis without previous heart failure who underwent endomyocardial biopsy. METHODS AND RESULTS: In our prospectively planned study SBP, DBP, mean arterial blood pressure (MAP) and ECGs on admission were analyzed retrospectively in 175 patients with suspected myocarditis, who underwent endomyocardial biopsy between 1994 and 2007. Patients were followed up for a median of 53 ±â€Š41 months, corresponding to a total follow-up of 9337 patient months. The primary endpoint was the time to cardiac death or heart transplantation, which occurred in 39 patients (22%). Baseline SBP was inversely associated with primary endpoint occurrence. Per 1 mmHg increase in SBP, the hazard ratio for the primary endpoint decreased by 4.3% [hazard ratio = 0.96, confidence interval (CI) = 0.94-0.98, P < 0.001]. The increased risk at a SBP below the mean value was confirmed after adjusting for the known independent predictors immunohistological signs of inflammation in biopsy samples, New York Heart Association functional class, and lack of ß-blocker treatment (hazard ratio = 2.78, CI = 1.25-6.18, P = 0.012). In the presence of all risk predictors, hazard ratio for primary endpoint was 4.97 (CI = 2.28-10.83, P < 0.001). In a subgroup analysis of patients without ß-blocker treatment, atrial fibrillation or pacemaker, a high heart rate was also associated with poor outcome (hazard ratio = 2.92, CI = 1.02-8.29, P = 0.045). CONCLUSION: In patients with suspected myocarditis without previous chronic heart failure low SBP, DBP and MAP were predictors of poor outcome. However, in patients not treated with ß-blockers, a high heart rate was a predictor for cardiac death or heart transplantation.

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

AIMS: 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. METHODS AND RESULTS: Cognitive performance, self-perceived quality of life, and depression were compared in 20 patients with decompensated CHF [ejection fraction (EF) 27 ± 8%, N-terminal pro brain natriuretic peptide (NT-proBNP) 10 880 pg/mL, interquartile range (4495-13 683)] before and after compensation, 20 age- and gender-matched stable CHF patients [New York Heart Association (NYHA) III-IV, EF 32 ± 10%, NT-proBNP 1881 pg/mL (323-1502)], and 20 healthy controls (EF 70 ± 5%). Patients with decompensated CHF showed significantly poorer performance in terms of short-term memory, working memory, executive control, and processing speed (P < 0.05) compared with stable CHF patients. Compensation improved the cognitive performance of decompensated CHF patients up to the level of patients with stable CHF. Compared with healthy controls, both patient groups were affected with respect to episodic memory (P < 0.0001) and fluid intelligence (P < 0.01). CONCLUSION: Decompensated heart failure patients are highly impaired in cognitive functioning, which improves but does not normalize after compensation. Neuropsychological diagnostics delivers important details for daily life activities and might identify individuals deserving special care.

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).

Prognostic electrocardiographic parameters in patients with suspected myocarditis.

AIMS: 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. METHODS AND RESULTS: Between 1995 and 2009, 186 consecutive patients (age: 43.4 ± 13.9 years) acutely admitted with clinically suspected myocarditis were enrolled and followed up for a mean of 55.1 ± 105.1 months. Electrocardiograms recorded before myocardial biopsy were analysed for rhythm, conduction times, signs of hypertrophy, and repolarization abnormalities. The primary endpoint was time to cardiac death or heart transplantation. The mean QRS duration was 90.3 ± 24.3 ms; 158 patients had a normal QRS duration (<120 ms) and 21 patients had a prolonged QRS duration (≥ 120 ms). During follow-up, 15.8% of patients with a normal QRS duration reached the primary endpoint compared with 42.8% of patients with a prolonged baseline QRS duration [hazard ratio (HR) 3.43; 95% confidence interval (CI) 1.78-6.01; P < 0.001]. The increased risk predicted by a prolonged QRS duration was robust after adjusting for covariates (HR 2.83; CI 1.07-7.49; P = 0.012). A QTc prolongation ≥ 440 ms (P = 0.011), an abnormal QRS axis (P = 0.012), and premature ventricular beats (P = 0.018) were significant monovariate predictors but did not prove to be independent predictors for survival in multivariate analysis. Q-waves and repolarization abnormalities were neither associated with the primary endpoint nor with immunohistological signs of inflammation. Other ECG parameters were not significantly related to outcome. CONCLUSION: A prolonged QRS duration is an independent predictor for cardiac death or heart transplantation in patients with suspected myocarditis.

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.

Functional effects of ß1-adrenoceptor polymorphisms on the hemodynamic response to dobutamine with and without ß-blocker administration.

BACKGROUND: The relevance of the Arg389Gly- and Ser49Gly-ß1-adrenoceptor (AR) polymorphisms for cardiovascular function and pharmacotherapy is controversial. METHODS: Out of 38 healthy male volunteers who were screened for both types of the ß1-AR polymorphism 23 subjects underwent dobutamine stress echocardiography at baseline, after administration of metoprolol succinate (n = 18, 190 mg/day) and 44 h after abrupt termination of the ß-blocker (n = 17). Heart rate (HR), systolic blood pressure (SAP), HR-corrected left ventricular circumferential fiber shortening (VCF(C)), cardiac output (CO), systemic vascular resistance (SVR) and left ventricular end-systolic meridional wall stress (EsMWS) were measured. ß1-AR gene polymorphisms were analyzed by TaqMan-PCR. RESULTS: Genotype frequency distributions and allele frequencies of the Gly389Arg and Ser49Gly polymorphisms of the ß1-AR were similar to published data. Although body surface area was similar for Arg/Arg subjects and Gly carriers the latter group revealed smaller left ventricular end-diastolic (-0.4 cm, p = 0.04) and end-systolic LV dimensions (-0.4 cm, p = 0.01). During dobutamine stimulation before, during and after termination of metoprolol coadministration no significant effect of the Arg389Gly-ß1-AR polymorphism on HR, SAP, CO and VCF(c) was detected. In contrast, SVR (p = 0.01) and EsMWS (p = 0.04) were significantly higher in Arg/Arg subjects. The VCF(C)-EsMWS regressions were similar for both groups, but revealed a minutely higher baseline contractility in the Arg/Arg group (p < 0.01). The ß1-AR Ser49Gly polymorphism had no effect on any of the measured parameters. CONCLUSIONS: Although the Arg389Gly-ß1-AR polymorphism has only minor relevance for LV contractility it may impact left ventricular size and afterload. The Ser49Gly-ß1-AR polymorphism has no relevant effect on LV geometry or function.

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.