Acute changes in cardiac dimensions, function, and longitudinal mechanics in healthy individuals with and without high-altitude induced pulmonary hypertension at 4559 m.

BACKGROUND: High-altitude pulmonary hypertension (HAPH) has a prevalence of approximately 10%. Changes in cardiac morphology and function at high altitude, compared to a population that does not develop HAPH are scarce. METHODS: Four hundred twenty-one subjects were screened in a hypoxic chamber inspiring a FiO2  = 12% for 2 h. In 33 subjects an exaggerated increase in systolic pulmonary artery pressure (sPAP) could be confirmed in two independent measurements. Twenty nine of these, and further 24 matched subjects without sPAP increase were examined at 4559 m by Doppler echocardiography including global longitudinal strain (GLS). RESULTS: SPAP increase was higher in HAPH subjects (∆ = 10.2 vs. ∆ = 32.0 mm Hg, p < .001). LV eccentricity index (∆ = .15 vs. ∆ = .31, p = .009) increased more in HAPH. D-shaped LV (0 [0%] vs. 30 [93.8%], p = .00001) could be observed only in the HAPH group, and only in those with a sPAP ≥50 mm Hg. LV-EF (∆ = 4.5 vs. ∆ = 6.7%, p = .24) increased in both groups. LV-GLS (∆ = 1.2 vs. ∆ = 1.1 -%, p = .60) increased slightly. RV end-diastolic (∆ = 2.20 vs. ∆ = 2.7 cm2 , p = .36) and end-systolic area (∆ = 2.1 vs. ∆ = 2.7 cm2 , p = .39), as well as RA end-systolic area index (∆ = -.9 vs. ∆ = .3 cm2 /m2 , p = .01) increased, RV-FAC (∆ = -2.9 vs. ∆ = -4.7%, p = .43) decreased, this was more pronounced in HAPH, RV-GLS (∆ = 1.6 vs. ∆ = -.7 -%, p = .17) showed marginal changes. CONCLUSIONS: LV and LA dimensions decrease and left ventricular function increases at high-altitude in subjects with and without HAPH. RV and RA dimensions increase, and RV longitudinal strain increases or remains unchanged in subjects with HAPH. Changes are negligible in those without HAPH.

Detection of early cardiac disease manifestation in propionic acidemia - Results of a monocentric cross-sectional study.

BACKGROUND: In propionic acidemia (PA) myocardial involvement is common and includes development of cardiomyopathy, life-threatening acute heart failure, and acquired long-QT syndrome. We sought to investigate which echocardiographic parameters of left ventricular systolic and diastolic function indicate early cardiac disease manifestation in PA. METHODS: This is a prospective observational study (cross-sectional design) in a Tertiary Medical Care Center. Individuals with confirmed PA were enrolled and the following cardiac investigations were performed in all study individuals: echocardiographic measurements of systolic and diastolic left ventricular (LV) function (LV fractional shortening (LV-FS), LV ejection fraction by biplane modified Simpson's (LV-EF), mitral annular plane systolic excursion (MAPSE), LV global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE), pulsed Doppler analyses of mitral valve (MV) inflow velocities (MV E/A) and MV deceleration time (DT-E), tissue doppler imaging (TDI) of the mitral annulus (MV E/e'), and LV myocardial performance index (LV-MPI)). LV and left atrial (LA) diameters were assessed. 12­lead electrocardiograms (ECG) were recorded and corrected QT intervals (QTc) calculated. Clinical phenotype and laboratory parameters at the time of cardiac investigation were assessed. Besides descriptive analyses we analyzed frequency, onset, and combinations of echocardiographic and ECG data as well as their correlations with clinical and biochemical findings. The effects of 'age at visit' and LV functional parameters on QTc were analyzed with multiple regression. RESULTS: A total of 18 patients with confirmed PA were enrolled. Median age at PA onset was 6 days (range 1-357 days). Median age at visit for cardiac evaluation was 13.1 years (range 0.6-28.1 years). LV-GLS was abnormal in 72.2%, LV-EF in 61.1%, MAPSE in 50%, MV E/e' in 44.4%, LV-MPI in 33.3%, LV-FS in 33.3%, and MV E/A in 27.8%. In cases with normal or near normal LV-FS, LV-GLS was pathological in 5/10, LV-EF in 4/10, and MAPSE in 3/10. The probability of developing LV dysfunction - systolic and diastolic - increases with age. LV-MPI is a reliable parameter to indicate systolic LV-dysfunction in combination with a dilated LV, i. e. dilated cardiomyopathy (DCM) in PA. Multiple regression reveals a significant positive association between LV diameters and QTc. Abnormal LV-GLS significantly correlates with reduced muscle strength, muscle tone and/or abnormal gross motor function. CONCLUSIONS: Our data suggests a high prevalence of cardiac disease manifestation in PA, considerably higher than in previous studies, where only LV-FS was used to assess LV function. Usage of advanced echocardiographic techniques, such as LV-GLS assessment, may allow for early detection of subtle LV dysfunction in PA, and may lead to timely cardiac treatment but also consideration of liver transplantation to prevent development of manifest cardiac complications.

Initial experience with percutaneous mitral valve repair in patients with cardiac amyloidosis.

BACKGROUND: Percutaneous mitral valve repair (PMVR) is a therapeutic option for severe mitral regurgitation (MR) in patients with heart failure due to differential aetiologies. However, only little is known about the safety and efficacy of this procedure in patients with amyloid cardiomyopathy. METHODS: Five patients with cardiac amyloidosis and moderate to severe or severe MR undergoing PMVR were analysed retrospectively and compared to seven patients with cardiac amyloidosis and severe MR without intervention. Clinical and functional data, renal function and cardiac biomarkers as well as established risk scores for cardiac amyloidosis were assessed. Primary endpoint was the reduction in MR one year after PMVR. Secondary endpoints were safety, overall mortality after 12 months compared with the control group, as well as changes in clinical and functional parameters. RESULTS: Amyloidosis risk assessment documented amyloid cardiomyopathy at an advanced stage in all patients. Procedural, technical and device success of PMVR were all 100% and residual MR remained mild to moderate at 12 months follow-up (P = .038 vs before PMVR). Differences in survival compared with the control (no PMVR) group pointed to a possible survival benefit in the PMVR group (P = .02). CONCLUSION: PMVR is a feasible and safe procedure in patients with cardiac amyloidosis and might carry a possible survival benefit in this patient group.

Percutaneous repair of severe mitral valve regurgitation secondary to chordae rupture in octogenarians using MitraClip.

OBJECTIVES: The aim of this study was to assess feasibility and clinical effectiveness of the MitraClip device in octogenarians suffering from severe mitral valve regurgitation due to chordae rupture. BACKGROUND: The MitraClip procedure is a suitable technique in high-risk surgical patients to achieve safe and effective percutaneous repair of mitral valve regurgitation. Octogenarians show cumulative risk and social aspects hindering mitral valve surgery. No data exists regarding the use of the MitraClip device in high-risk octogenarians suffering from mitral valve chordae rupture. METHODS: Between October 2009 and March 2017 98 high-risk octogenarians (society of thoracic surgeons score [STS]: 9.7% ± 0.8) with mitral valve prolapse and consecutively chordae rupture were treated with the MitraClip after interdisciplinary discussion. RESULTS: Successful mitral valve repair was achieved in 91% of the octogenarians. Repair of the mitral valve caused immediate and significant reduction of dyspnoea (NYHA class: 3.5 ± 0.4 vs 2.0 ± 0.3; P < 0.001), cardiac reverse remodeling (LVESD: 39 ± 0.8 vs 35 ± 0.8; P < 0.01) and amelioration of cardiac biomarkers (NTproBNP (4884 ± 52 ng/L vs 2473 ± 210 ng/L; P < 0.05,). Effects were stable over the 12 months observation period. None of our patients died intraprocedurally. CONCLUSIONS: Percutaneous repair of chordae rupture is feasible and safe in high-risk octogenarians. The MitraClip should be considered to repair severe mitral valve regurgitation due to mitral valve chordae rupture in high-risk octogenarians after interdisciplinary discussion even facing a challenging anatomy.

Heavy drinkers of Ilex paraguariensis beverages show lower lipid profiles but higher body weight.

Obesity is a widely recognized risk factor for several diseases, reaching an epidemic magnitude worldwide. Natural polyphenols may improve blood lipids and body weight, but their clinical relevance in the general population remains unclear. Thus, we aimed to analyze the relationship of intake of Ilex paraguariensis (I. paraguariensis) beverages to lipid profiles and body weight in a large patient population. Patients were recruited to participate in an educational program to change habits to a healthy lifestyle. Anamnesis, clinical and laboratory assessments were conducted at study enrollment and during follow­up. I. paraguariensis beverages were defined according to preparation as obtained by repeated cold water extraction (CWE), hot water infusions, or water and sugar decoction. Heavy drinkers were defined as those persons consuming >1 L/day of one or more preparation types. Participants (N = 18,287) aged ≥18 years entered the study. Overall prevalence of I. paraguariensis consumption was 91.2%. All three forms were drunk by 35.7%, whereas CWE + hot water infusion and CWE alone by 28.4% and 14.5% participants, respectively. Heavy CWE drinkers had lower total cholesterol (191.4 ± 49.4 vs. 194.6 ± 48.3 mg/dl, p = .02) and lower low­density lipoprotein cholesterol (118.6 ± 38.9 vs. 121.2 ± 47.1 mg/dl, p = .001), but body weight was higher (81.1 ± 16.8 vs. 77.2 ± 16.4 kg, p < .0001) compared with moderate drinkers. Fasting glucose was lower (104.5 ± 48.7 vs. 107.2 ± 49.5 mg/dl, p < .001), and consumption of carbohydrates was higher (36.3% vs. 28.7%, p < .001). A low­lipids high­body­weight paradox could be observed in a population of heavy drinkers of I. paraguariensis beverages. Induced hypoglycemia and compensatory higher intake of refined carbohydrates may represent a possible cause.

Percutaneous repair of mitral valve regurgitation in patients with severe heart failure: comparison with optimal medical treatment.

BACKGROUND: Occurrence of severe mitral valve (MV) regurgitation (MR) is an independent negative predictor of mortality in patients with severe systolic heart failure (HF). This study examines clinical effects and cardiac reverse remodelling in patients with severe systolic HF receiving percutaneous mitral valve repair (PMVR) using MitraClip in comparison to patients receiving optimal medical therapy only. METHODS: Between 2010 and 2014, 86 patients (Society of Thoracic Surgeons score: 10.5% ± 1.2%) with severe HF (left ventricular [LV] ejection fraction; LVEF: 25% ± 2%; LV endsystolic diameter [LVESD]: 55 ± 3 mm) and severe MR received PMVR using MitraClip. Cardiac reverse remodelling and clinical parameters were compared to HF patients with severe MR (from our HF outpatient clinic; n = 69; LVEF: 26% ± 1.4%; LVESD: 53 ± 2 mm) receiving optimal medical therapy (OMT) only. All patients received stable OMT and were characterised by echocardiography, 6-minwalk-distance test and cardiac biomarkers within a 24 months observation period. RESULTS: PMVR in patients with end-stage HF and severe MR resulted in reduction of MR and significant additional cardiac reverse remodelling (LVEF: 26 ± 1.4 vs. 33% ± 2%, p < .05; LVESD: 53 ± 2 vs. 47 ± 2 mm, p < .05) over the 24 months observation period as compared to pharmacologically-only managed comparators. CONCLUSIONS: Both OMT and PMVR cause cardiac reverse remodelling and relief of symptoms in patients with HF and severe MR. PMVR results in significant additional cardiac reverse remodelling compared to pharmacologically-only managed patients.

Regional differences in prognostic value of cardiac valve plane displacement in systemic light-chain amyloidosis.

BACKGROUND: To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis. METHODS: Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments. RESULTS: We identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSEanterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ2 = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p < 0.0001). AAPSE added incremental prognostic power to an imaging prediction model of late gadolinium enhancement and global longitudinal strain (GLS) (∆χ2 = 5.8, p = 0.02) as well as to a clinical model including Karnofsky index and NT-proBNP (∆χ2 = 6.2, p = 0.01). CONCLUSION: In patients with cardiac involvement in AL amyloidosis, systolic CVPD obtained from standard long axis cine views appear to indicate outcome better, when obtained in the anterior aortic plane (AAPSE) and provide incremental prognostic value to LGE and strain measurements.

Atlas of the clinical genetics of human dilated cardiomyopathy.

AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. METHODS AND RESULTS: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. CONCLUSION: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.

Biomarker changes after strenuous exercise can mimic pulmonary embolism and cardiac injury--a metaanalysis of 45 studies.

BACKGROUND: Biomarkers are well established for diagnosis of myocardial infarction [cardiac troponins, high-sensitivity cardiac troponins (hs-cTn)], exclusion of acute and chronic heart failure [B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP)] and venous thromboembolism (d-dimers). Several studies have demonstrated acute increases in cardiac biomarkers and altered cardiac function after strenuous sports that can pretend a cardiovascular emergency and interfere with state-of-the-art clinical assessment. METHODS: We performed a systematic review and metaanalysis of biomarker and cardiovascular imaging changes after endurance exercise. We searched for observational studies published in the English language from 1997 to 2014 that assessed these biomarkers or cardiac function and morphology directly after endurance exercise. Of 1787 identified abstracts, 45 studies were included. RESULTS: Across all studies cardiac troponin T (cTnT) exceeded the cutoff value (0.01 ng/mL) in 51% (95% CI, 37%-64%) of participants. The measured pooled changes from baseline for high-sensitivity cTnT (hs-cTnT) were +26 ng/L (95% CI, 5.2-46.0), for cTnI +40 ng/L (95% CI, 21.4; 58.0), for BNP +10 ng/L (95% CI, 4.3; 16.6), for NT-proBNP +67 ng/L (95% CI, 49.9; 84.7), and for d-dimer +262 ng/mL (95% CI, 165.9; 358.7). Right ventricular end diastolic diameter increased and right ventricular ejection fraction as well as the ratio of the early to late transmitral flow velocities decreased after exercise, while no significant changes were observed in left ventricular ejection fraction. CONCLUSIONS: Current cardiovascular biomarkers (cTnT, hs-cTnT, BNP, NT-proBNP, and d-dimer) that are used in clinical diagnosis of pulmonary embolism, acute coronary syndrome, and heart failure are prone to alterations due to strenuous exercise. Hence, it is necessary to take previous physical exercise into account when a cardiac emergency is suspected.

[Prevalence of cardiovascular risk factors in an urban ambulatory adult population: AsuRiesgo study, Paraguay]. / Prevalencia de factores de riesgo cardiovascular en una población adulta ambulatoria urbana: estudio AsuRiesgo, Paraguay.

OBJECTIVE: Cardiovascular diseases are the leading cause of mortality in the world. Although most of them are preventable, their prevalence continues to increase. The objective of this study was to estimate the prevalence of cardiovascular risk factors in an urban ambulatory adult hospital population in Asunción, Paraguay. METHODS: A cross-sectional study was undertaken in the population of patients enrolled in the AsuRiesgo prospective study on the prevention of cardiovascular disease, which focuses on promoting a healthy lifestyle. Patients 18 years of age or older who were encountered in doctors' waiting rooms in a tertiary care hospital were invited to participate. Each patient's clinical history, body measurements, and laboratory test results were obtained. RESULTS: A total of 18 287 patients aged 51 ± 16 years were recruited. Of this group, 67.5% were female, with an average bodyweight of 77.5 ± 16.2 kg and a body mass index 29.7 ± 5.9 kg/m². The prevalence rates of a history of myocardial infarction, stroke, diabetes mellitus, and hypertension were 2.6%, 3%, 13.3%, and 53%, respectively, and the rates of smoking, unhealthy diet, sedentary lifestyle, and psychological stress were 29.3%, 41.2%, 58.2%, and 56.6%. The overall prevalence of obesity and overweight was 79.6%; the rates of prehypertension and systemic hypertension were 39% and 25%, respectively; and the prevalence of metabolic syndrome was 34.7%. CONCLUSIONS: Although the prevalence rates of smoking, systemic hypertension, and diabetes mellitus were low, those for obesity, sedentary lifestyle, psychological stress, unhealthy diet, and metabolic syndrome were very high. This finding demonstrates the need for global action to prevent disability and death from ischemic heart and cerebrovascular disease. It is urgent to implement programs to address these challenges on a national scale.

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy.

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788 mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238 mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.

Prognosis of light chain amyloidosis: a multivariable analysis for survival prediction in patients with cardiac involvement proven by endomyocardial biopsy.

BACKGROUND: Cardiac involvement is a main determinant of mortality in light chain (AL) amyloidosis but data on survival of patients with cardiac AL amyloidosis proven by endomyocardial biopsy (EMB) are sparse. METHODS: This study analysed clinical, laboratory, electrocardiography and echocardiographic parameters for their prognostic value in the assessment of patients with AL amyloidosis and cardiac involvement. Patients with AL amyloidosis who had their first visit to the amyloidosis centre at the University Hospital Heidelberg between 2006 and 2017 (n=1628) were filtered for cardiac involvement proven by EMB. In the final cohort, mortality-associated markers were analysed by univariate and multivariable Cox regression. Cut-off values for each parameter were calculated using the survival time. RESULTS: One-hundred and seventy-four patients could be identified. Median overall survival time was 1.5 years and median follow-up time was 5.2 years. At the end of the investigation period, 115 patients had died. In multivariable analysis, New York Heart Association-functional class >II (HR 1.65; 95% CI 1.09 to 2.50; p=0.019), left ventricular global longitudinal strain (HR 1.12; 95% CI 1.03 to 1.22; p=0.007), left ventricular end-systolic volume (HR 1.02; 95% CI 1.01 to 1.03; p=0.001), systolic pulmonary artery pressure (HR 0.98; 95% CI 0.96 to 0.99; p=0.027), N-terminal pro-B-type natriuretic peptide (HR 1.57; 95% CI 1.17 to 2.11; p=0.003) and difference in free light chains (HR 1.30; 95% CI 1.05 to 1.62; p=0.017) were independently predictive. CONCLUSION: Among all patients with AL amyloidosis those with cardiac involvement represent a high-risk population with limited therapy options. Therefore, accurate risk stratification is necessary to identify cardiac amyloidosis patients with favourable prognosis. Incorporation of modern imaging techniques into existing or newly developed scoring systems is a promising option that might enable the implementation of risk-adapted therapeutic strategies.

Surgical Rehearsal for Mitral Valve Repair: Personalizing Surgical Simulation by 3D Printing.

PURPOSE: The goal of this study was to show possible effects of performing the actual procedure of mitral valve repair (MVR) on personalized silicone models 1 day before operation. DESCRIPTION: Based on preoperative 3-dimensional echocardiography recordings, flexible 3-dimensional replicas of the depicted pathologic mitral valves could be produced and used for a simulation of reconstructive techniques analogous to the upcoming MVR procedure. We integrated this step of personalized surgical planning into the clinical routine of 6 MVR cases with 3 different surgeons. This pilot study was assessed by evaluating questionnaires and by comparing isolated surgical steps with conventional MVRs. EVALUATION: This approach was considered a better preparation for MVRs with overall positive responses from the surgeons. Simulation helped reduce the time of initial inspection of the valve because of better understanding of the valve's pathomorphologic features. Annuloplasty benefited from preoperative sizing by reducing the number of sizing attempts. CONCLUSIONS: These initial findings suggest that simulation-based surgical planning can be implemented into patients' and physicians' clinical workflow as a major technologic advancement for future MVR preparation.

Evaluation of Right Ventricular Function in Patients with Propionic Acidemia-A Cross-Sectional Study.

(1) Background: In propionic acidemia (PA), myocardial involvement often leads to progressive cardiac dysfunction of the left ventricle (LV). Cardiomyopathy (CM) is an important contributor to mortality. Although known to be of prognostic value in CM, there are no published data on right ventricular (RV) function in PA patients. (2) Methods: In this cross-sectional single-center study, systolic and diastolic RV function of PA patients was assessed by echocardiography, including frequency, onset, and combinations of echocardiographic parameters, as well as correlations to LV size and function. (3) Results: N = 18 patients were enrolled. Tricuspid annulus S' was abnormal in 16.7%, RV-longitudinal strain in 11.1%, tricuspid annular plane systolic excursion (TAPSE) in 11.1%, Tricuspid valve (TV) E/e' in 33.3%, and TV E/A in 16.7%. The most prevalent combinations of pathological parameters were TV E/A + TV E/e' and TAPSE + TV S'. With age, the probability of developing abnormal RV function increases according to age-dependent normative data. There is a significant correlation between TAPSE and mitral annular plane systolic excursion (MAPSE), and RV/LV-longitudinal strain (p ≤ 0.05). N = 5 individuals died 1.94 years (mean) after cardiac evaluation for this study, and all had abnormal RV functional parameters. (4) Conclusions: Signs of diastolic RV dysfunction can be found in up to one third of individuals, and systolic RV dysfunction in 16.7% of individuals in our cohort. RV function is impaired in PA patients with a poor outcome. RV functional parameters should be used to complement clinical and left ventricular echocardiographic findings.

Safety of Stress Cardiac Magnetic Resonance in Patients With Moderate to Severe Aortic Valve Stenosis.

BACKGROUND: Dobutamine and adenosine stress cardiac magnetic resonance (CMR) imaging is relatively contraindicated in patients with moderate to severe aortic valve stenosis (AS). We aimed to determine the safety of dobutamine and adenosine stress CMR in patients with moderate to severe AS. METHODS: In this retrospective study patients with AS who underwent either dobutamine or adenosine stress CMR for exclusion of obstructive coronary artery disease were enrolled. We recorded clinical data, CMR and echocardiography findings, and complications as well as minor symptoms. Patients with AS were compared to matched individuals without AS. RESULTS: A total of 187 patients with AS were identified and compared to age-, gender- and body mass index-matched 187 patients without AS. No severe complications were reported in the study nor the control group. The reported frequency of non-severe complications and minor symptoms were similar between the study and the control groups. Nineteen patients with AS experienced non-severe complications or minor symptoms during dobutamine stress CMR compared to eighteen patients without AS (p = 0.855). One patient with AS and two patients without AS undergoing adenosine stress CMR experienced minor symptoms (p = 0.562). Four examinations were aborted because of chest pain, paroxysmal atrial fibrillation and third-degree atrioventricular block. Inducible ischaemia, prior coronary artery bypass grafting, prior stroke and age were associated with a higher incidence of complications and minor symptoms. CONCLUSIONS: Moderate to severe AS was not associated with complications during CMR stress test. The incidence of non-severe complications and minor symptoms was greater with dobutamine.

Functional improvement following direct interventional leaflet repair of severe tricuspid regurgitation.

AIMS: Several new percutaneous tricuspid repair systems have recently been introduced as new treatment options for severe tricuspid regurgitation (TR). Clinical improvement following percutaneous tricuspid valve leaflet repair has been demonstrated by recent studies. A possible impact on exercise capacity has not yet been reported. METHODS AND RESULTS: Eleven patients with at least severe TR and successful tricuspid leaflet repair using the PASCAL Ace implant at our cardiology department were included in this analysis. All patients suffered from symptomatic right-sided heart failure with compromised exercise capacity. Cardiopulmonary exercise testing (CPET), clinical, laboratory, and echocardiographic parameters were assessed at baseline and 3 months follow-up. The primary endpoint was the change in maximal oxygen consumption [VO2 max (mL/(min*kg))] at 3 months follow-up. Secondary endpoints included improvement in TR, cardiac biomarkers, and other clinical outcomes. TR severity at 3 months follow-up post-PASCAL Ace implantation was significantly lower than at baseline (P = 0.004). Cardiac biomarkers including high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide as well as right ventricular diameter improved slightly without reaching statistical significance (P = 0.89, P = 0.32, and P = 0.06, respectively). PASCAL Ace implantation resulted in a significant improvement in cardiopulmonary exercise capacity at 3 months follow-up compared with baseline. Mean VO2 max improved from 9.5 ± 2.8 to 11.4 ± 3.4 mL/(min*kg) (P = 0.006), VO2 max per cent predicted from 42 ± 12% to 50 ± 15% (P = 0.004), peak oxygen uptake from 703 ± 175 to 826 ± 198 mL/min (P = 0.004), and O2 pulse per cent predicted from 67 ± 21% to 81 ± 25% (P = 0.011). Other CPET-related outcomes did not show any significant change over time. CONCLUSIONS: In this single-centre retrospective analysis, direct tricuspid valve leaflet repair using the transcatheter PASCAL Ace implant system was associated with a reduced TR severity and improved cardiopulmonary exercise capacity.

Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure and Preserved Ejection Fraction.

BACKGROUND: Coexistence of atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) is common, affecting morbidity and prognosis. This study evaluates outcome after cryoballoon ablation for AF in HFpEF compared with patients without heart failure. METHODS: A total of 102 AF patients with left ventricular ejection fraction ≥50% undergoing cryoballoon ablation were prospectively enrolled. Baseline evaluation included echocardiography, stress echocardiography, 6-minute walk test, biomarkers, and quality of life assessment (Short-Form-36). Procedural parameters and clinical, functional and echocardiographic end points at follow-up ≥12 months after AF ablation were compared between patients with and without HFpEF. RESULTS: Patients with HFpEF (n=24) were older (median, 74 years versus 65 years; P=0.001) more often female (83% versus 28%; P<0.001) and characterized by more pronounced AF-related symptoms (median European Heart Rhythm Association score 3 versus 2; P<0.001), higher left atrial pressures (median, 14 mm Hg versus 10 mm Hg; P=0.008), reduced left atrial-appendage velocity (median, 36 cm/s versus 59 cm/s; P<0.001), and reduced distance in the 6-minute walk test (median, 488 m versus 539 m; P<0.001). Patients with HFpEF more often experienced AF recurrence (57% versus 23%; P=0.003), repeat AF ablation (39% versus 14%; P=0.01) and AF-related rehospitalization (26% versus 7%; P=0.016). Heart failure symptoms and elevated cardiac biomarkers persisted, even in patients with HFpEF with successful rhythm control at follow-up. Echocardiographic follow-up showed progression of adverse left atrial remodeling and no relevant improvement in diastolic function in HFpEF. Quality of life improved in patients without HFpEF, whereas patients with HFpEF still exhibited a lower physical component summary score (median, 41.5 versus 53.4; P<0.004). CONCLUSIONS: Patients with HFpEF constitute a distinct subgroup with elevated risk for AF recurrence after cryoballon ablation. Functional hallmarks of HFpEF persist, irrespective of rhythm status at follow-up. Future research is needed to optimize treatment strategies in patients with HFpEF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04317911.

Impact of Homoarginine on Myocardial Function and Remodeling in a Rat Model of Chronic Renal Failure.

PURPOSE: Low plasma concentrations of the amino acid homoarginine (HA) have been shown to correlate with adverse cardiovascular outcome, particularly in patients with chronic kidney disease. The present study sought to investigate the effect of HA treatment on cardiac remodeling in rats undergoing artificially induced renal insufficiency by 5/6 nephrectomy (5/6 Nx). METHODS: A total of 33 male Wistar rats were randomly divided into sham and 5/6 Nx groups, receiving either placebo treatment or 400 mg·kg-1·day-1 HA over a 4-week period. RESULTS: 5/6 Nx per se resulted in adverse myocardial remodeling with aggravated cardiac function and associated cardiac overload as the most obvious alteration (-23% ejection fraction, P < 0.0001), as well as increased myocardial fibrosis (+80%, P = 0.0005) compared to placebo treated sham animals. HA treatment of 5/6 Nx rats has led to an improvement of ejection fraction (+24%, P = 0.0003) and fractional shortening (+21%, P = 0.0126), as well as a decrease of collagen deposition (-32%, P = 0.0041), left ventricular weight (-14%, P = 0.0468), and myocyte cross-sectional area (-12%, P < 0.0001). These changes were accompanied by a downregulation of atrial natriuretic factor (-65% P < 0.0001) and collagen type V alpha 1 chain (-44%, P = 0.0006). Sham animals revealed no significant changes in cardiac function, myocardial fibrosis, or any of the aforementioned molecular changes after drug treatment. CONCLUSION: Dietary HA supplementation appears to have the potential of preventing cardiac remodeling and improving heart function in the setting of chronic kidney disease. Our findings shed new light on HA as a possible new therapeutic agent for patients at high cardiovascular risk.

Large atrial thrombus formation after MitraClip implantation: is anticoagulation mandatory?

Percutaneous mitral valve repair with the MitraClip system has evolved as a promising new technique for the non-surgical treatment of mitral regurgitation (MR). To date, few major adverse events have been reported in initial studies with this technique. The case is reported of a 70-year-old patient who underwent successful MitraClip implantation. Routine pre-discharge transesophageal echocardiography on day 5 after implantation showed large thrombus formation in the left atrium (posterolateral wall) and on the right atrial side of the septum. The patient had not received any anticoagulation after clip implantation, and did not have any monitored episodes of atrial fibrillation prior to the scheduled discharge day. It is concluded that mandatory anticoagulation for at least one month should be considered in patients undergoing MitraClip implantation.

Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises?

Epigallocatechin-3-gallate (EGCG), the main and most significant polyphenol in green tea, has shown numerous health promoting effects acting through different pathways, as antioxidant, anti-inflammatory and anti-atherogenic agent, showing gene expression activity, functioning through growth factor-mediated pathways, the mitogen-activated protein kinase-dependent pathway, the ubiquitin/proteasome degradation pathway, as well as eliciting an amyloid protein remodeling activity. However, epidemiological inferences are sometimes conflicting and in vitro and in vivo studies may seem discrepant. Current knowledge on how to enhance bioavailability could be the answer to some of these issues. Furthermore, dose levels, administration frequency and potential side effects remain to be examined.