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.

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.

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.

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.

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.

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 > or =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 cm(2) versus 1.0+/-0.2 cm(2), 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.

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.

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 beta-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 beta-blocker therapy, but not histology (positive Dallas criteria) or viral genome detection, are related to poor outcome.

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.

Carvedilol but not metoprolol reduces beta-adrenergic responsiveness after complete elimination from plasma in vivo.

BACKGROUND: Carvedilol but not metoprolol exhibits persistent binding to beta-adrenergic receptors (beta-ARs) even after washout in cell culture experiments. Here, we determined the significance of this phenomenon on human beta-ARs in vitro and in vivo. METHODS AND RESULTS: Experiments were conducted on human atrial trabeculae (n=8 to 10 per group). In the presence of metoprolol, isoproterenol potency was reduced compared with controls (P<0.001). In the presence of carvedilol, isoproterenol identified 2 distinct binding sites of high (36+/-6%; -8.8+/-0.4 log mol/L) and low affinity (-6.5+/-0.2 log mol/L). After beta-blocker washout, isoproterenol potency returned to control values in metoprolol-treated muscles, whereas in carvedilol-treated preparations, isoproterenol potency remained decreased (P<0.001 versus control). In vivo studies were performed in 9 individuals receiving metoprolol succinate (190 mg/d) or carvedilol (50 mg/d) for 11 days in a randomized crossover design. Dobutamine stress echocardiography (5 to 40 microg x kg(-1) x min(-1)) was performed before, during, and 44 hours after application of study medication. Beta-blocker medication reduced heart rate, heart rate-corrected velocity of circumferential fiber shortening, and cardiac output compared with baseline (P<0.02 to 0.0001). After withdrawal of metoprolol, all parameters returned to baseline values, whereas after carvedilol, all parameters remained reduced (P<0.05 to 0.001) despite complete plasma elimination of carvedilol. CONCLUSIONS: Carvedilol but not metoprolol inhibits the catecholamine response of the human heart beyond its plasma elimination. The persistent beta-blockade by carvedilol may be explained by binding of carvedilol to an allosteric site of beta-ARs.

Exercise programmes for patients with chronic heart failure.

The safety and efficacy of exercise training in patients with chronic heart failure (CHF) have been reported in a large number of scientific studies, with endurance training representing the most frequently applied training stimulus. Beneath the common continuous method of endurance training, the interval method (short bouts of intense exercise interspersed with pre-scheduled rest intervals), was also applied in some studies. Ergometric testing is a prerequisite for all individualised training prescription and is an appropriate method of efficacy documentation. However, there is a surprisingly large range of exercise intensities being prescribed to patients with CHF. Most of the prescription models refer to maximal ergometric measurements. Submaximal references from lactate and ventilatory curves represent an alternative method in measuring accuracy and efficacy of training. The course of heart rate during submaximal incremental exercise can be reliably used to indicate endurance gains in CHF. Some positive reports exist for carefully executed strength endurance training for patients with CHF and there are convincing arguments for the use of coordination and flexibility exercises; however, substantial scientific evidence is lacking.

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.

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.

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.