Impact of telemedical management on hospitalization and mortality in heart failure patients with diabetes: a post-hoc subgroup analysis of the TIM-HF2 trial.

BACKGROUND: The TIM-HF2 study demonstrated that remote patient management (RPM) in a well-defined heart failure (HF) population reduced the percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death during 1-year follow-up (hazard ratio 0.80) and all-cause mortality alone (HR 0.70). Higher rates of hospital admissions and mortality have been reported in HF patients with diabetes compared with HF patients without diabetes. Therefore, in a post-hoc analysis of the TIM-HF2 study, we investigated the efficacy of RPM in HF patients with diabetes. METHODS: TIM-HF2 study was a randomized, controlled, unmasked (concealed randomization), multicentre trial, performed in Germany between August 2013 and May 2018. HF-Patients in NYHA class II/III who had a HF-related hospital admission within the previous 12 months, irrespective of left ventricular ejection fraction, and were randomized to usual care with or without added RPM and followed for 1 year. The primary endpoint was days lost due to unplanned cardiovascular hospitalization or due to death of any cause. This post-hoc analysis included 707 HF patients with diabetes. RESULTS: In HF patients with diabetes, RPM reduced the percentage of days lost due to cardiovascular hospitalization or death compared with usual care (HR 0.66, 95% CI 0.48-0.90), and the rate of all-cause mortality alone (HR 0.52, 95% CI 0.32-0.85). RPM was also associated with an improvement in quality of life (mean difference in change in global score of Minnesota Living with Heart Failure Questionnaire score (MLHFQ): - 3.4, 95% CI - 6.2 to - 0.6). CONCLUSION: These results support the use of RPM in HF patients with diabetes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01878630.

Impact of ACE I gene insertion/deletion, A-240T polymorphisms and the renin-angiotensin-aldosterone system on COVID-19 disease.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19. METHODS: Our preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19. RESULTS: Our study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels. CONCLUSIONS: Although there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response. CLINICAL TRIAL REGISTRATION: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020.

[Telemedicine in chronic heart failure-From clinical studies to standard care]. / Telemedizin bei chronischer Herzinsuffizienz ­ von klinischen Studien zur Regelversorgung.

Telemedicine has the potential to solve many current and especially future challenges in medical care. Using the example of heart failure (HF), the transition of telemedicine from clinical studies to standard care is presented. In patients with chronic HF, randomized controlled trials have shown that telemedicine-based care leads to a reduction in mortality and cardiovascular morbidity. Based on these data, the Federal Joint Committee (G-BA) decided that for the first time a digital method should be introduced into standard care for high-risk patients with reduced left ventricular ejection fraction. In the future, this group of patients will be entitled to telemedical care using active rhythm devices or noninvasive measuring devices. The indications are assessed by the primary treating physician (PBA), who works together with a telemedicine center (TMZ) managed through cardiology that receives daily telemetric data and notifies the PBA of abnormal findings. Alternatively, a cardiologist PBA with an associated TMZ infrastructure can also provide telemedical care. In the future, advanced technologies such as artificial intelligence or mobile communication standard 5G will help to make telemedicine both widely available and usable for alternative sensor technology.

Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial.

BACKGROUND: Remote patient management in patients with heart failure might help to detect early signs and symptoms of cardiac decompensation, thus enabling a prompt initiation of the appropriate treatment and care before a full manifestation of a heart failure decompensation. We aimed to investigate the efficacy of our remote patient management intervention on mortality and morbidity in a well defined heart failure population. METHODS: The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial was a prospective, randomised, controlled, parallel-group, unmasked (with randomisation concealment), multicentre trial with pragmatic elements introduced for data collection. The trial was done in Germany, and patients were recruited from hospitals and cardiology practices. Eligible patients had heart failure, were in New York Heart Association class II or III, had been admitted to hospital for heart failure within 12 months before randomisation, and had a left ventricular ejection fraction (LVEF) of 45% or lower (or if higher than 45%, oral diuretics were being prescribed). Patients with major depression were excluded. Patients were randomly assigned (1:1) using a secure web-based system to either remote patient management plus usual care or to usual care only and were followed up for a maximum of 393 days. The primary outcome was percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death, analysed in the full analysis set. Key secondary outcomes were all-cause and cardiovascular mortality. This study is registered with ClinicalTrials.gov, number NCT01878630, and has now been completed. FINDINGS: Between Aug 13, 2013, and May 12, 2017, 1571 patients were randomly assigned to remote patient management (n=796) or usual care (n=775). Of these 1571 patients, 765 in the remote patient management group and 773 in the usual care group started their assigned care, and were included in the full analysis set. The percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause death was 4·88% (95% CI 4·55-5·23) in the remote patient management group and 6·64% (6·19-7·13) in the usual care group (ratio 0·80, 95% CI 0·65-1·00; p=0·0460). Patients assigned to remote patient management lost a mean of 17·8 days (95% CI 16·6-19·1) per year compared with 24·2 days (22·6-26·0) per year for patients assigned to usual care. The all-cause death rate was 7·86 (95% CI 6·14-10·10) per 100 person-years of follow-up in the remote patient management group compared with 11·34 (9·21-13·95) per 100 person-years of follow-up in the usual care group (hazard ratio [HR] 0·70, 95% CI 0·50-0·96; p=0·0280). Cardiovascular mortality was not significantly different between the two groups (HR 0·671, 95% CI 0·45-1·01; p=0·0560). INTERPRETATION: The TIM-HF2 trial suggests that a structured remote patient management intervention, when used in a well defined heart failure population, could reduce the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality. FUNDING: German Federal Ministry of Education and Research.

Left atrial strain predicts hemodynamic parameters in cardiovascular patients.

BACKGROUND: We aimed to evaluate the predictive value of left atrial (LA) reservoir, conduit, and contractile function parameters as assessed by speckle tracking echocardiography (STE) for invasively measured hemodynamic parameters in a patient cohort with myocardial and valvular diseases. METHODS: Sixty-nine patients undergoing invasive hemodynamic assessment were enrolled into the study. Invasive hemodynamic parameters were obtained by left and right heart catheterization. Transthoracic echocardiography assessment of LA reservoir, conduit, and contractile function was performed by STE. RESULTS: Forty-nine patients had sinus rhythm (SR) and 20 patients had permanent atrial fibrillation (AF). AF patients had significantly reduced LA reservoir function compared to SR patients. In patients with SR, LA reservoir, conduit, and contractile function inversely correlated with pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure, and mean pulmonary artery pressure (PAP), and showed a moderate association with cardiac index. In AF patients, there were no significant correlations between LA reservoir function and invasively obtained hemodynamic parameters. In SR patients, LA contractile function with a cutoff value of 16.0% had the highest diagnostic accuracy (area under the curve, AUC: 0.895) to predict PCWP ≥18 mm Hg compared to the weaker diagnostic accuracy of average E/E' ratio with an AUC of 0.786 at a cutoff value of 14.3. In multivariate analysis, LA contractile function remained significantly associated with PCWP ≥18 mm Hg. CONCLUSION: In a cohort of patients with a broad spectrum of cardiovascular diseases LA strain shows a valuable prediction of hemodynamic parameters, specifically LV filling pressures, in the presence of SR.

Improved Left Ventricular Structure and Function After Successful Kidney Transplantation.

BACKGROUND/AIMS: Cardiac changes observed in chronic kidney disease patients are of multifactorial origin including chronic uremia, hemodynamics or inflammation. Restoration of renal function by kidney transplantation (KTX) may reverse cardiac changes. Novel echocardiographic methods such as speckle tracking echocardiography (STE) allow early and sensitive detection of subtle changes of cardiac parameters. We evaluated changes of cardiac structure and function after KTX by advanced echocardiographic modalities. METHODS: Thirty-one KTX recipients (female n=11) were evaluated by medical examination, laboratory testing and echocardiography before and after KTX (median follow-up 19 months). Left ventricular (LV) and right ventricular (RV) diameters and function were assessed by echocardiographic standard parameters. Longitudinal 2D strain of the LV (GLPS) and left atrium (LA) was determined by 2D STE. RESULTS: After KTX, median serum creatinine level was 1.3 mg/dl (IQR, 1.2-1.5). Systolic blood pressure decreased significantly after KTX. Echocardiography showed a significant reduction in LV end-diastolic septal and posterior wall thickness and LV mass index after KTX, which was accompanied by an improvement of GLPS. There were no relevant changes in parameters of LA (reservoir, conduit or contractile) function, LV diastolic or RV function after KTX. CONCLUSION: LV hypertrophy reversed after successful KTX and was accompanied by an improvement in longitudinal LV function as assessed by STE. Diastolic function and STE-derived LA function parameters did not change significantly after KTX.

Midterm echocardiographic follow-up of cardiac function after living kidney donation.

BACKGROUND: Living kidney donation (LKD) has become increasingly important as more patients reach end-stage renal disease. While safety of the donor is of utmost importance, recent data have suggested an increased risk for cardiovascular mortality after LKD. Therefore, we assessed the changes of cardiac structure and function after LKD by advanced echocardiographic methods. METHODS: 30 living kidney donors were evaluated by medical examination, laboratory testing, and echocardiography before and after LKD (median follow-up 19.5 months). Left ventricular (LV) and right ventricular (RV) function was assessed by echocardiographic standard indices. Longitudinal 2D strain of the LV and left atrium (LA) was determined by 2D speckle tracking. RESULTS: Serum creatinine increased significantly from 0.80 ± 0.12 mg/dL to 1.18 ± 0.21 mg/ dL (p < 0.001) after LKD. There was a trend to higher blood pressure after LKD, accompanied with significantly higher intake of antihypertensive drugs. Echocardiographic parameters of LV, LA, and RV function did not change significantly after LKD. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels remained within normal ranges after LKD. CONCLUSION: The rise in serum creatinine and blood pressure indicates that patients have a potentially higher cardiac risk after LKD. However, our pilot study found no evidence for detrimental effects of LKD on cardiac structure and function within a relatively short-term follow-up.

Cardiac and renal function in a large cohort of amateur marathon runners.

BACKGROUND: Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. METHODS: A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). RESULTS: Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. CONCLUSIONS: The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

Echocardiographic follow-up of patients with systemic sclerosis by 2D speckle tracking echocardiography of the left ventricle.

BACKGROUND: Subclinical myocardial involvement is common in systemic sclerosis (SSc) and associated with poor prognosis. Early detection, particularly during follow-up, is important. Two-dimensional speckle tracking echocardiography (STE) has already been shown to detect early left ventricular systolic impairment in SSc patients with advanced disease. The aim of this study was to assess the ability of STE to diagnose changes in left ventricular function in patients with SSc with preserved LV ejection fraction (LVEF) and normal pulmonary pressure over time. METHODS: This single-center pilot study included nineteen SSc patients without pulmonary hypertension and preserved LVEF (55.2 ± 10.8 years, 13 women, mean modified Rodnan Skin Score of 8.2 ± 6.5, median disease duration 6 ± 4.5 years). We performed STE at baseline and after two years (mean 756.6 ± 8.8 days). Pulmonary hypertension was ruled out in all patients by right heart catheterization (average mean PAP 17.7 ± 3.5 mmHg). RESULTS: The LVEF remained unchanged (63.3 ± 4.2% vs. 63.2 ± 5.0%, P = ns), but the global longitudinal peak systolic strain of the left ventricle was significantly lower: baseline -22.0 ± 2.3% vs. follow-up -20.8 ± 2.1% (P = 0.04). The regional analysis showed a heterogeneous distribution of segmental systolic dysfunction that did not match any particular coronary artery distribution. In contrast, the LV diastolic function remained stable during follow-up. CONCLUSION: STE might be a sensititive and valuable method to detect early LV systolic impairment in patients with SSc and preserved LVEF during two years. Prospective evaluations are needed for prognostic implications of these changes.

Increased longitudinal contractility and diastolic function at rest in well-trained amateur Marathon runners: a speckle tracking echocardiography study.

BACKGROUND: Regular physical activity reduces cardiovascular risk. There is concern that Marathon running might acutely damage the heart. It is unknown to what extent intensive physical endurance activity influences the cardiac mechanics at resting condition. METHODS: Eighty-four amateur marathon runners (43 women and 41 men) from Berlin-Brandenburg area who had completed at least one marathon previously underwent clinical examination and echocardiography at least 10 days before the Berlin Marathon at rest. Standard transthoracic echocardiography and 2D strain and strain rate analysis were performed. The 2D Strain and strain rate values were compared to previous published data of healthy untrained individuals. RESULTS: The average global longitudinal peak systolic strain of the left ventricle was -23 +/- 2% with peak systolic strain rate -1.39 +/- 0.21/s, early diastolic strain rate 2.0 +/- 0.40/s and late diastolic strain rate 1.21 +/- 0.31/s. These values are significantly higher compared to the previous published values of normal age-adjusted individuals. In addition, no age-related decline of longitudinal contractility in well-trained athletes was observed. CONCLUSIONS: There is increased overall longitudinal myocardial contractility at rest in experienced endurance athletes compared to the published normal values in the literature indicating a preserved and even supra-normal contractility in the athletes. There is no age dependent decline of the longitudinal 2D Strain values. This underlines the beneficial effects of regular physical exercise even in advanced age.

Long-term Doppler hemodynamics and effective orifice areas of Edwards SAPIEN and medtronic CoreValve prostheses after TAVI.

BACKGROUND: Although initial hemodynamics of percutaneously implanted aortic bioprostheses compare favorably to surgically implanted valves, the durability of the flow characteristics remains unknown. As biological prostheses are at potential risk for early degeneration, the aim of our study was to compare Doppler hemodynamics and effective orifice area (EOA) directly after and at least 1 year after valve implantation. METHODS: In this monocentric, prospective study, we determined peak velocity, peak and mean systolic gradients, and EOA by echocardiography in 75 patients (Edwards SAPIEN, n = 20; CoreValve, n = 55) 1 week (median 7 ± 25 days) and 1 year (median 378 ± 157 days, maximum 1034 days) after transcatheter aortic valve implantation (TAVI). RESULTS: After 12 months, Doppler performance of the aortic valve prostheses remained unchanged. The peak instantaneous velocity was 1.9 ± 0.4 m/s directly after TAVI versus 1.8 ± 0.5 m/s (P = ns) at follow-up, with a mean gradient of 8.5 ± 3.7 mmHg and 8.1 ± 4.2 (P = ns), respectively. Interestingly, the degree of mitral regurgitation (MR) decreased significantly (P = 0.007) over time, and the severity of aortic regurgitation (AR) remained unchanged during follow-up (P = ns). CONCLUSION: For at least 1 year after TAVI, the excellent Doppler hemodynamics and EOA are preserved in transcatheter aortic valve prostheses, and the severity of MR decreased significantly. In addition, we found no evidence of early valve deterioration or progression of AR.

mRNA vaccines for COVID-19 are safe and clinically effective in patients with cardiac amyloidosis.

INTRODUCTION: Amyloidosis is a rare disease in which malformed proteins are deposited in tissues occurring mostly commonly in older age. These deposits can lead to severe organ dysfunction e.g. in the myocardium with great impact on prognosis. The Covid-19 pandemic has caused excess mortality worldwide since 2020. Risk factors for a severe course include pre-existing cardiac diseases like heart failure and advanced age. Therefore, vaccination against Sars-CoV2 viruses is highly recommended for patients with cardiac amyloidosis. However, since there are no specific data on mRNA vaccines in patients with cardiac amyloidosis, some patients have concerns about cardiac adverse events following immunization (AEFI), such as myocarditis. PURPOSE: The purpose of the study is to assess the safety and efficacy of mRNA vaccines in patients with cardiac amyloidosis. METHODS: Patients of the Amyloidosis Center Charité Berlin (ACCB) were assessed about the vaccination, its tolerability and clinical effectiveness. To date, we included 62 patients (54 men) with a median age of 82,5 years (range 37 to 92). 46 patients had wtATTR amyloidosis, ten patients had hATTR amyloidosis, and six patients had AL amyloidosis. The mean systolic left ventricular function was 51% (range 30 to 62) with a mean global strain of -11,5% (range -18,5 to -3,1). The mean NT-pro-BNP was 1145 ng/l (range 24 to 48297). RESULTS: 59 patients were triple vaccinated and three patients so far are double vaccinated. Three of the patients were unvaccinated. 171 of the vaccine doses administered were mRNA vaccines and eight doses were a viral vector-vaccine. None of the patients reported severe side effects. Thirteen patients reported feeling of pressure and pain at the injection site after vaccination and four patients had fever of maximum two days, eight patients reported lower general condition of maximum five days. One patient reported malaise for 14 days after each vaccination, which resolved spontaneously. There was no clinical or laboratory evidence of suspected vaccine-induced myocarditis. Five patients reported of a COVID-19 breakthrough infection, all of which with a mild course of disease. None of the patients had symptoms of worsening heart failure in temporal relation to the vaccination. Most of the vaccinations (103) were performed at an official vaccination center, 59 were performed at a general practitioner. CONCLUSION: In patients with cardiac amyloidosis, mRNA vaccines for COVID-19 are safe with respect to severe cardiac adverse events and show effective protection against clinically relevant SARS-CoV2 infection.

Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real-World Data.

BACKGROUND: Results from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy) indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR-CA). However, real-world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR-CA treated with tafamidis in a real-world setting and assess the prognostic role of the New York Heart Association (NYHA) classification. METHODS AND RESULTS: We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR-CA (wild-type or variant) treated with tafamidis. Clinical outcome was tracked through follow-up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan-Meier analysis estimated overall and MACE-free survival including NYHA subgroups (NYHA I/II versus NYHA III). One hundred sixty-seven patients with ATTR-CA (94.6% wild-type) were enrolled and followed for a median of 539 [323-869] days. Median overall survival was not reached. Estimated 1-year, 2-year, and 5-year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (P=0.002). Median MACE-free survival time was 1082 (95% CI, 962-1202) days. MACE-free survival was higher in the NYHA I/II subgroup (P<0.001). With respective hazard ratios of 5.85 (95% CI, 1.48-23.18; P=0.012) and 3.95 (95% CI, 1.99-7.84; P<0.001), NYHA III was an independent predictor of death and MACE. CONCLUSIONS: Treatment of ATTR-CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a reliable tool to provide patients with individualized prognostic information.

Diagnostic value of papillary muscle hypertrophy and mitral valve thickness to discriminate cardiac amyloidosis and Fabry disease.

BACKGROUND: Cardiac amyloidosis (CA) and Fabry disease (FD) cause myocardial damage but may also affect the valvular and subvalvular apparatus. We aimed to evaluate the diagnostic accuracy of new echocardiographic indices including mitral valve thickness and papillary muscle (PM) hypertrophy to differentiate CA and FD. METHODS: In patients with confirmed CA and FD, a detailed assessment of valvular function, mitral valve leaflet thickness and PM area as well as PM left ventricular area ratio (PM/LV-ratio) was performed in offline analyses. Receiver operating characteristic curve analyses were conducted to determine the diagnostic accuracy of mitral valve thickness, PM hypertrophy, and PM/LV-ratio to distinguish CA from FD. RESULTS: We retrospectively analyzed a cohort of 129 patients (FD n = 49, CA n = 80). CA patients showed significantly more thickened mitral valve leaflets (4.1 ± 1.3 mm vs. 2.9 ± 1.1 mm, p < 0.001) and a higher PM area [4.0 (3.1-4.6) mm2 vs. 2.8 (2.1-4.6) mm2, p = 0.009] with a comparable PM/LV-ratio in both groups. Mitral valve thickness showed the highest diagnostic accuracy to discriminate CA [AUC 0.77 (95% CI 0.67-0.87)]. The prevalence of aortic, tricuspid, and pulmonary valve regurgitation was significantly higher in CA (aortic regurgitation ≥ II° 13% vs. 4%, tricuspid regurgitation≥ II° 19% vs. 8%, p < 0.001). CONCLUSION: Our results suggest that the assessment of mitral valve thickness may be a new useful echocardiographic parameter to differentiate CA and FD, whereas papillary muscle hypertrophy and PM/LV-ratio showed a limited diagnostic performance to discriminate CA. German clinical trials registry: DRKS00027403.

Right heart and left atrial strain to differentiate cardiac amyloidosis and Fabry disease.

Echocardiographic differentiation of cardiac amyloidosis (CA) and Fabry disease (FD) is often challenging using standard echocardiographic parameters. We retrospectively analyzed the diagnostic accuracy of right heart and left atrial strain parameters to discriminate CA from FD using receiver operating characteristic curve analyses and logistic regression models. A total of 47 FD and 88 CA patients with left ventricular wall thickening were analyzed. The comparison of both cardiomyopathies revealed significantly reduced global and free wall longitudinal right ventricular strain (RVS; global RVS: CA - 13 ± 4%, n = 67, vs. FD - 18 ± 4%, n = 39, p < 0.001) as well as right atrial strain (RAS; reservoir RAS: CA 12 ± 8%, n = 70, vs. FD 26 ± 9%, n = 40, p < 0.001) and left atrial strain (LAS) in CA patients. Individually, global RVS as well as phasic LAS and RAS showed the highest diagnostic accuracy to distinguish CA and FD. The best diagnostic accuracy was achieved by combining the age, basal RV diameter, global RVS, and reservoir and conduit RAS (area under the curve 0.96 [95% CI 0.90-1.00]). Differential echocardiographic diagnostic work-up of patients with suspected CA or FD can be improved by integrating structural and functional parameters of the right heart and the left atrium.Trial registration: DRKS00027403.

Neurological affection and serum neurofilament light chain in wild type transthyretin amyloidosis.

In contrast to inherited transthyretin amyloidosis (A-ATTRv), neuropathy is not a classic leading symptom of wild type transthyretin amyloidosis (A-ATTRwt). However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt, A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charité Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels. 16 out of 73 (21.9%) patients presented with a severe neuropathy which we defined by a Neuropathy Impairment Score (NIS) of 20 or more. In this group, quality of life was reduced, peripheral neuropathy was more severe, and spinal stenosis and joint replacements were frequent. Age- and BMI matched serum NFL levels were markedly elevated in patients with a NIS ≥ 20. We therefore conclude that highly abnormal values in neuropathy scores such as the NIS occur in A-ATTRwt, and have an important impact on quality of life. Both peripheral neuropathy and spinal canal stenosis are likely contributors. Serum NFL may serve as a biomarker for neurological affection in patients with A-ATTRwt. It will be important to consider neurological aspects of A-ATTRwt for diagnosis, clinical follow-up, and future treatment development.

Diagnostic value of left ventricular layer strain and specific regional strain patterns in cardiac amyloidosis and Fabry disease.

Aims: Layer-specific left ventricular (LV) strain alterations have been suggested as a specific finding in Fabry disease (FD). Our study aimed to assess the diagnostic value of layer-specific radial strain (RS) indices compared to the established LV regional strain pattern in cardiac amyloidosis (CA) and FD, i.e. apical sparing and posterolateral strain deficiency (PLSD). Methods and results: We retrospectively analysed the global, subendocardial, subepicardial LV radial strain, the corresponding strain gradient, as well as the regional and global longitudinal strain. The diagnostic accuracy of the diverse LV strain analyses was comparatively assessed using receiver operating characteristic curve and multivariable regression analyses. In 40 FD and 76 CA patients, CA featured more reduced layer strain values [global RS -12.3 (-15.6 to -9.6) in CA vs. -16.7 (-20.0 to -13.6) in FD; P < 0.001; subendocardial RS -22.3 (-27.4 to -15.9) vs. -28.3 (-31.8 to -23.6), P < 0.001; subepicardial RS -6.6 (-8.6 to -4.7) in CA vs. -8.9 (-11.7 to - 6.5) in FD; P < 0.001]. Global radial and longitudinal strain held an area under the curve (AUC) of 0.75 (0.66-0.84) and AUC 0.73 (0.63-0.83). While the apical sparing and PLSD strain pattern showed the highest accuracy as single parameters [AUC 0.87 (0.79-0.95) and 0.81 (0.72-0.89), P < 0.001], the combination of subendocardial RS and the apical sparing pattern featured the highest diagnostic accuracy [AUC 0.92 (0.87-0.97)]. Conclusion: Combining radial strain-derived parameters to the established strain pattern apical sparing and PLSD improve the diagnostic accuracy in the echocardiographic assessment in suspected storage disease.

Early clinical outcomes of Portico and Edwards Sapien 3 valve prosthesis in transcatheter aortic valve replacement: propensity-matched analysis.

Introduction: There is a lack of real-world data directly comparing different valve prostheses for transaortic valve replacement (TAVR). We aimed to compare early clinical outcomes at 30-days between the self-expandable Portico valve (Abbott) with the balloon-expandable Edwards Sapien 3 valve (Edwards Lifesciences) (ES3). Methods: Out of 1,901 patients undergoing TAVR between January 2018 and December 2021, all patients who received either Portico valve or ES3 valve via transfemoral TAVR were matched using nearest-neighbor (1:1) propensity scoring. Primary endpoints were single safety endpoints and early safety composite endpoints defined by Valve Academic Research Consortium-2 (VARC-2) criteria. The secondary endpoint was to analyze risk predictors for new permanent pacemaker (PPM) implantation in TAVR. Results: Out of 661 complete cases, a total of 434 patients were successfully matched based on age, sex, Euro Score II and STS-score. In the matched cohort, 217 received either a Portico or valve and 217 received an ES3 valve. The VARC-2 early safety composite scores indicated a significantly greater overall 30-day safety risk in the Portico group at 9.2% (n = 20) compared to 3.7% (n = 8) in the ES3 group (p = 0.032). The requirement for new permanent pacemaker (PPM) implantation was also higher in the Portico group, at 21.2% (n = 46) vs. 13.4% (n = 29) in the ES3 group (p = 0.042). 30-day mortality was higher was 3.7% (n = 8) in Portico group compared to 0.9% in ES3 group (p = 0.11). Furthermore, implantation of the Portico valve was identified as a significant risk predictor for new PPM implantation, alongside higher age, preprocedural atrioventricular block (AVB) and longer total procedure duration. Conclusion: This study shows significantly higher rates of early clinical complications for Portico valve prostheses compared to ES3. These findings should be especially taken into consideration when selecting valve prosthesis for high-risk patients.

From Videogames to Teaching - Different Camera Perspectives in an Interactive Synchronous Online Tutorial.

The global COVID-19 pandemic has required clinical skills training to be transferred to an online format. An interactive synchronous online tutorial with different camera perspectives was developed. In a survey, 79% of the students preferred the first-person perspective, which allowed students to view the abdominal examination through the examiner's eyes.

Gaze patterns reflect and predict expertise in dynamic echocardiographic imaging.

Purpose: Echocardiography is the most important modality in cardiac imaging. Rapid valid visual assessment is a critical skill for image interpretation. However, it is unclear how skilled viewers assess echocardiographic images. Therefore, guidance and implicit advice are needed for learners to achieve valid image interpretation. Approach: Using a signal detection approach, we compared 15 certified experts with 15 medical students in their diagnostic decision-making and viewing behavior. To quantify attention allocation, we recorded eye movements while viewing dynamic echocardiographic imaging loops of patients with reduced ejection fraction and healthy controls. Participants evaluated left ventricular ejection fraction and image quality (as diagnostic and visual control tasks, respectively). Results: Experts were much better at discriminating between patients and healthy controls ( d ' of 2.58, versus 0.98 for novices). Eye tracking revealed that experts fixated diagnostically relevant areas earlier and more often, whereas novices were distracted by visually salient task-irrelevant stimuli. We show that expertise status can be almost perfectly classified either based on judgments or purely on eye movements and that an expertise score derived from viewing behavior predicts diagnostic quality. Conclusions: Judgments and eye tracking revealed significant differences between echocardiography experts and novices that can be used to derive numerical expertise scores. Experts have implicitly learned to ignore the salient motion cue presented by the mitral valve and to focus on the diagnostically more relevant left ventricle. These findings have implications for echocardiography training, objective characterization of echocardiographic expertise, and the design of user-friendly interfaces for echocardiography.