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The impact of tafamidis on myocardial strain in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) have been barely investigated. We aimed to determine tafamidis-induced changes using serial speckle tracking echocardiography and to identify imaging parameters for specific therapy monitoring.ATTR-CM patients underwent serial TTE with two-dimensional (2 D) speckle tracking imaging. Patients receiving tafamidis free acid 61 mg (Treatment with tafamidis free acid 61 mg in ATTR-CM patients delays the deterioration of LA and LV longitudinal function, resulting in significant clinical benefits compared with natural history. Serial TTE with 2 D speckle tracking imaging may be appropriate for disease-specific therapy monitoring.

Aims The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF. Methods and Results The phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicentre DYNAMIC trial assessed riociguat in PH-HFpEF. Patients were recruited at five hospitals across Austria and Germany. Key eligibility criteria were mean pulmonary artery pressure ≥25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction ≥50%. Patients were randomized to oral treatment with riociguat or placebo (1:1). Patients started at 0.5 mg three times daily (TID) and were up-titrated to 1.5 mg TID. The primary efficacy endpoint was change from baseline to week 26 in cardiac output (CO) at rest, measured by right heart catheterization. Primary efficacy analyses were performed on the full analysis set. Fifty-eight patients received riociguat and 56 patients placebo. After 26 weeks, CO increased by 0.37 ± 1.263 L/min in the riociguat group and decreased by −0.11 ± 0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval 0.112, 0.971; P = 0.0142). Five patients dropped out due to riociguat-related adverse events but no riociguat-related serious adverse event or death occurred. Conclusion The vasodilator riociguat improved haemodynamics in PH-HFpEF. Riociguat was safe in most patients but led to more dropouts as compared to placebo and did not change clinical symptoms within the study period.

Background For patients after acute myocardial infarction, a gap exists in Austrian care in the early period following hospital discharge. The patients’ and their relatives’ perspectives are crucial for developing nursing interventions. Objective To investigate patients’ and their relatives’ experiences from the onset of acute myocardial infarction symptoms until the early period following hospital discharge. Methods This qualitative study used in-depth individual and couple interviews with acute myocardial infarction patients (n = 14) and their relatives (n = 7) for data collection and a phenomenological hermeneutical analysis method. Results Four phenomena, i.e., “Understanding of living with heart disease,” “Omnipresent anxiety,” “Being there for each other,” and “Being understood as an individual,” showed participants’ needs. “Understanding of living with heart disease” described the process participants underwent to understand coronary heart disease, including the sub-phenomena of “Perceiving having heart disease,” “Getting familiar with heart disease,” and “Living life against the backdrop of heart disease.” It implied the participants’ strong need to get information on disease causes at the individual level and reshape their lives after the event to ensure a normal life. Conclusion Healthcare professionals should involve patients and their relatives in care and provide communication based on their needs. Such endeavors may allow those affected to understand coronary heart disease and prepare for and adapt to the needed lifestyle changes. Nursing interventions that consider the four phenomena highlighted in this study may ensure enhanced care for those affected in their lives after acute myocardial infarction, improving nursing care quality.

Background With the introduction of several drugs for the therapy of transthyretin-related amyloidosis (ATTR) which slow down the disease, early detection of polyneuropathy (PNP) is becoming increasingly of interest. [99mTc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) bone scintigraphy, which is used for the diagnosis of cardiac (c)ATTR, can possibly make an important contribution in the identification of patients at risk for PNP. Methods Fifty patients with cATTR, who underwent both planar whole-body DPD scintigraphy and nerve conduction studies (NCS) were retrospectively evaluated. A subgroup of 22 patients also underwent quantitative SPECT/CT of the thorax from which Standardized Uptake Values (SUVpeak) in the subcutaneous fat tissue of the left axillar region were evaluated. Results The Perugini score was significantly increased in patients with cATTR and additional diagnosis of PNP compared to patients without (2.51 ± 0.51 vs 2.13 ± 0.52; P = 0.03). Quantitative SPECT/CT revealed that DPD uptake in the subcutaneous fat of the left axillar region was significantly increased in cATTR patients with compared to patients without (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04). Conclusion This study suggests that DPD bone scintigraphy is a useful tool for identification of patients with cATTR and a risk for PNP due to increased DPD soft tissue uptake.

Aims Tafamidis treatment positively affects left ventricular (LV) structure and function and improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). We aimed to investigate the relationship between treatment response and cardiac amyloid burden identified by serial quantitative 99mTc-DPD SPECT/CT. We furthermore aimed to identify nuclear imaging biomarkers that could be used to quantify and monitor response to tafamidis therapy. Methods and results Forty wild-type ATTR-CM patients who underwent 99mTc-DPD scintigraphy and SPECT/CT imaging at baseline and after treatment with tafamidis 61 mg once daily [median, 9.0 months (interquartile range 7.0–10.0)] were divided into two cohorts based on the median (−32.3%) of the longitudinal percent change in standardized uptake value (SUV) retention index. ATTR-CM patients with a reduction greater than or equal to the median (n = 20) had a significant decrease in SUV retention index (P < 0.001) at follow-up, which translated into significant benefits in serum N-terminal prohormone of brain natriuretic peptide levels (P = 0.006), left atrial volume index (P = 0.038), as well as LV [LV global longitudinal strain: P = 0.028, LV ejection fraction (EF): P = 0.027, LV cardiac index (CI): P = 0.034] and right ventricular (RV) [RVEF: P = 0.025, RVCI: P = 0.048] functions compared with patients with a decrease less than the median (n = 20). Conclusion Treatment with tafamidis in ATTR-CM patients results in a significant reduction in SUV retention index, associated with significant benefits for LV and RV function and cardiac biomarkers. Serial quantitative 99mTc-DPD SPECT/CT imaging with SUV may be a valid tool to quantify and monitor response to tafamidis treatment in affected patients. Translational perspective 99mTc-DPD SPECT/CT imaging with determination of SUV retention index as part of a routine annual examination can provide evidence of treatment response in ATTR-CM patients receiving disease-modifying therapy. Further long-term studies with 99mTc-DPD SPECT/CT imaging may help to evaluate the relationship between tafamidis-induced reduction in SUV retention index and outcome in patients with ATTR-CM and will demonstrate whether highly disease-specific 99mTc-DPD SPECT/CT imaging is more sensitive than routine diagnostic monitoring.

Aim Patients with heart failure with reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, and poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy and tolerability in patients with SBP ≤100 mmHg enrolled in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF). Methods and results The GALACTIC-HF enrolled patients with baseline SBP ≥85 mmHg with a primary outcome of time to cardiovascular death or first heart failure event. In this analysis, patients were divided according to their baseline SBP (≤100 vs. >100 mmHg). Among the 8232 analysed patients, 1473 (17.9%) had baseline SBP ≤100 mmHg and 6759 (82.1%) had SBP >100 mmHg. The primary outcome occurred in 715 (48.5%) and 2415 (35.7%) patients with SBP ≤100 and >100 mmHg, respectively. Patients with lower SBP were at higher risk of adverse outcomes. Omecamtiv mecarbil, compared with placebo, appeared to be more effective in reducing the primary composite endpoint in patients with SBP ≤100 mmHg [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70–0.94] compared with those with SBP >100 mmHg (HR, 0.95; 95% CI, 0.88–1.03; P-value for interaction = 0.051). In both groups, omecamtiv mecarbil did not change SBP values over time and did not increase the risk of adverse events, when compared with placebo. Conclusion In GALACTIC-HF, risk reduction of heart failure outcomes with omecamtiv mecarbil compared with placebo was large and significant in patients with low SBP. Omecamtiv mecarbil did not affect SBP and was well tolerated independent of SBP values.

Zusammenfassung Hintergrund Menschen nach akutem Koronarsyndrom weisen weiterhin ein hohes kardiovaskuläres Risiko auf. Eine pflegerische Intervention zur Verbesserung der Adhärenz von Betroffenen hinsichtlich der empfohlenen Präventionsmaßnahmen ist erforderlich. In deren Entwicklung sollen alle an der Versorgung beteiligten Personengruppen miteinbezogen werden, u. a. Gesundheitsexpertinnen und -experten. Ziel Ziel war es, die Ausrichtung eines dem österreichischen Kontext angepassten pflegegeleiteten Sekundärpräventionsprogramms für Menschen nach akutem Koronarsyndrom aus Sicht von Gesundheitsexpertinnen und -experten zu generieren. Methodik Die Entwicklung dieses Programms stützt sich methodisch auf das „intervention mapping“. Um die Inhalte der ersten 3 Schritte des Intervention mapping zu erarbeiten, wurden 2 Fokusgruppeninterviews und 13 Einzelinterviews mit 27 Gesundheitsexpertinnen und -experten durchgeführt. Die Datenanalyse erfolgte anhand der thematischen Analyse nach Braun und Clarke. Ergebnisse Die Ausrichtung des Programms bezieht sich auf die Bereiche „personenzentrierter Ansatz“, „Akutkrankenhaus als Initialpunkt“ und „persönliches Gespräch als zentrale Vermittlungsform“. Die erforderlichen strukturellen und personellen Rahmenbedingungen umfassen „Prioritätensetzung für die Patientenedukation im Akutkrankenhaus“, „Einrichtung einer Anlaufstelle“, „interdisziplinäre Zusammenarbeit“ und „gesetzliche Bestimmungen für die Patienteninformation“ sowie die Schaffung der Position einer „cardiac rehabilitation nurse“, welche speziell ausgebildetes Pflegepersonal übernehmen könnte. Ein vertieftes Krankheitsverständnis und ein reduzierter Angstzustand sollen die angestrebten Ergebnisse des Programms sein. Schlussfolgerung Das zu entwickelnde Programm kann dazu dienen, die nichtmedikamentöse Sekundärprävention bei den Betroffenen im Akutkrankenhaus zu initiieren und nach der Entlassung fortzuführen. Als Rahmenbedingungen müssen eine Anlaufstelle und die Funktion einer Cardiac rehabilitation nurse geschaffen werden. Somit kann diese spezialisierte Pflegeperson die Betroffenen in der Übergangsphase begleiten, während sie die Patientenedukation unter dem personenzentrierten Ansatz durchführt.

Objectives The aim of this study was to assess the effect of the wearable cardioverter-defibrillator (WCD) on patient-reported outcomes (PRO) in adult patients with high risk for sudden cardiac arrest. Methods We performed a systematic literature search in Medline (via PubMed) and Cochrane Library in February 2022 and included studies with a study population ≥18 years and prescribed WCD. PRO include health-related quality of life (QoL), symptoms, utilities, or satisfaction ratings. Study selection was done by two reviewers independently using predefined inclusion and exclusion criteria. Quality assessment of studies as well as data extraction was performed by one author and approved by a second author. Results of the included studies are presented quantitatively. Results One randomized controlled trial (RCT), one comparative non-randomized trial, and three single-arm trials were included. QoL was assessed in four studies, but with different assessment tools. One study additionally evaluated the change in depressive symptoms and anxiety and one study focused on acceptability of WCD but evaluated items that are closely related to QoL. Results of the RCT show no statistically significant difference in QoL assessed by SF-36 and EQ-5D comparing WCD and Guideline-Directed Medical Therapy (GDMT) versus GDMT alone. One comparative study reports an improvement in depressive symptoms and anxiety within groups but no significant difference between groups. Further, one single-arm study reported improvement in QoL between baseline and day 90 and day 180. Conclusions The available evidence demonstrates that the usage of WCD is not affecting PRO, like QoL, depressive symptoms or anxiety negatively.

BackgroundDiagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic abilities are limited.ObjectiveThe aim was to perform a thorough electrophysiological characterisation of patients with CA and derive an easy-to-use tool for diagnosis.MethodsWe applied electrocardiographic imaging (ECGI) to acquire electroanatomical maps in patients with CA and controls. A machine learning approach was then used to decipher the complex data sets obtained and generate a surface ECG-based diagnostic tool.FindingsAreas of low voltage were localised in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualised on the right ventricle. Potential maps revealed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1–V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in the inferior leads II, III and aVF. Respective surface ECG leads showed two characteristic patterns. Ten blinded cardiologists were asked to identify patients with CA by analysing 12-lead ECGs before and after training on the defined ECG patterns. Training led to significant improvements in the detection rate of CA, with an area under the curve of 0.69 before and 0.97 after training.InterpretationUsing a machine learning approach, an ECG-based tool was developed from detailed electroanatomical mapping of patients with CA. The ECG algorithm is simple and has proven helpful to suspect CA without the aid of advanced imaging modalities.

Background: In patients with transthyretin amyloid cardiomyopathy, tafamidis was shown to slow the decline in 6-minute walking distance as compared with placebo. We aimed to define the impact of tafamidis and optimal background treatment on functional capacity as determined by cardiopulmonary exercise testing (CPET). Methods: Seventy-eight consecutive patients were enrolled in the study. They underwent CPET at baseline, and outcome defined as death or heart failure hospitalization was obtained for a time period of up to 30 months. Fifty-four patients completed a follow-up CPET at 9±3 months (range, 4–16 months). Improvement in peak VO 2 at follow-up was defined as ∆peak VO 2 ≥1.0 mL/(kg·min), stable peak VO 2 was defined as 0≤∆peak VO 2 2 was defined by ∆peak VO 2 Results: Baseline peak VO 2 >14 mL/(kg·min) as well as minute ventilation/carbon dioxide production slope≤34 were associated with a lower risk of death or heart failure hospitalization ( P =0.002, P =0.007, respectively). In 54 patients, who received tafamidis and underwent repeat CPET testing, an improvement in physical performance ( P =0.002) was observed at follow-up. When comparing pre and post-treatment parameters, 29 patients (54%) showed an increase in percent predicted peak VO 2 ( P 2 ( P P 2 had less advanced heart disease at baseline ( P =0.046). Conclusions: Our findings demonstrate that baseline peak VO 2 and baseline minute ventilation/carbon dioxide production slope predict outcomes and an improvement in physical performance as measured by CPET was observed in patients receiving tafamidis, who had less advanced disease at baseline, emphasizing the importance of early diagnosis.

Background The Covid-19 pandemic has affected our lives for over a year and almost 500.000 people in Austria have been infected. Although many of them only had low or mild symptoms some had to be treated in the hospital. Even months after their infection some patients complain about fatigue, exercise intolerance and dyspnoea. The aim of this study was to perform a follow-up cardiopulmonary exercise test (CPET) on those patients, at 6 months after their hospitalization to find out if there are long-term cardio-pulmonary limitations (CPL) of Covid-19. We also wanted to check if there is any difference in outcome and CPL between patients who received oxygen therapy vs. without oxygen therapy. Methods 40 patients were included into this study (16 women = 40%; 24 men = 60%). All patients were hospitalized during their infection with Covid-19 (5 patients at ICU) and underwent CPET 6±2 month after discharge. 20 patients (50%) received oxygen therapy or ventilation during their hospitalization. CPET data were assessed at rest, during exercise and at recovery. Blood parameters including NT-pro BNP were collected and an interview and examination were performed. CPL was defined as VO2% of Predicted ≤84%, VE/CO2 Slope ≥34 and RER at peak of exercise ≥1.1. Results Median age of all patients was 46 years [interquartile range (IQR): 35.3–55.8], median BMI was 26.0 m2/kg [IQR: 23.0–29.0] and the median NTproBNP was 53.1 pg/mL [IQR: 24.0–95.6]. When comparing the two groups, we found higher percentage of CPL in patients who received oxygen therapy during their hospitalization (10% with oxygen vs. 5% without oxygen). Notably, the number of patients with a BMI ≥25 m2/kg was higher in the oxygen therapy group than in those without oxygen (80% vs. 45%). The median BMI without oxygen therapy was 24.0 [IQR: 20.3–26.8] vs. 29.0 [IQR: 25.0–31.0] with oxygen therapy (p=0.004). There were no significant differences in NT-proBNP levels (p=0.545). The median VO2% of predicted was 88.0% [72.5–98.0] without oxygen therapy vs. 84.5% [IQR: 70.8–91.8] with oxygen therapy (p=0.289), the median HR percentage of predicted was 92.5% [IQR: 85.5–97.8] without oxygen therapy vs. 94.5% [IQR: 88.3–103.5] with oxygen therapy (p=0.478), the median physical performance in watt in patients without oxygen therapy was 130.0 [IQR: 108.5–197.5] vs. 135.0 [IQR: 97.0–188.3] with oxygen therapy (p=0.820). Conclusion The findings of our study did not show any statistically significant difference in long-term CPL between patients who received oxygen therapy vs. those who didn't. Therefore, other causes of the exercise intolerance and dyspnoea have to be discussed multidisciplinary. Subclinical CPL in the absence of significant clinical symptoms represent a concern after a Covid-19 infection. Overall, 7.5% of our patients showed CPL although those patients didn't have any clinical symptoms. Therefore, CPET is a good method to discover asymptomatic patients with CPL. Funding Acknowledgement Type of funding sources: None.

SummaryThe prevalence and significance of cardiac amyloidosis have been considerably underestimated in the past; however, the number of patients diagnosed with cardiac amyloidosis has increased significantly recently due to growing awareness of the disease, improved diagnostic capabilities and demographic trends. Specific therapies that improve patient prognosis have become available for certain types of cardiac amyloidosis. Thus, the earliest possible referral of patients with suspicion of cardiac amyloidosis to an experienced center is crucial to ensure rapid diagnosis, early initiation of treatment, and structured patient care. This requires intensive collaboration across several disciplines, and between resident physicians and specialized centers. The aim of this consensus statement is to provide guidance for the rapid and efficient diagnosis and treatment of light-chain amyloidosis and transthyretin amyloidosis, which are the most common forms of cardiac amyloidosis.

Background Bone scintigraphy plays an important role in the diagnosis of cardiac Transthyretin-Related Amyloidosis (ATTR). The mechanism of myocardial tracer accumulation and its dependence over time are not fully understood. Recently, a scintigraphic quantification of the cardiac amyloid deposition has been discussed. Nevertheless, little is known regarding the right time of quantitative imaging. Methods The geometrical mean of decay corrected total counts over the heart and the heart/whole-body ratio (H/WB) were evaluated in 23 patients undergoing DPD-bone scan with planar whole-body images 1 and 3 hours post injection (p.i.). Myocardial standard uptake values (SUV)peak were assessed in another 15 patients with quantitative SPECT/CT imaging 1 hours and 3 hours p.i.. Results Total counts over the heart (1 hours p.i.: 81,676 cts, range 69,887 to 93,091 cts and 3 hours p.i.: 64,819 cts, range 52,048 to 86,123 cts, P = .0005) and H/WB ratio (1 hours p.i.:0.076 ± 0.020 and 3 hours p.i. 0.070 ± 0.022; P = .0003) were significantly increased 1 hours p.i.. Furthermore median myocardial SUVpeak (1 hours p.i.:12.2, range 9.6 to 18.9 and 3 hours p.i.: 9.6, range 8.2 to 15.0, P = 0.0012) was also significantly higher after 1 hours p.i. compared to 3 hours p.i.. Conclusion Cardiac DPD activity and myocardial SUVpeak are time-dependent, which should be considered when using quantitative bone scintigraphy in ATTR patients.

Background Pericardial and pleural effusion are common findings in patients with cardiac amyloidosis (CA). It is not known, whether effusions correlate with right ventricular (RV) function in these patients. Furthermore, data on the prognostic significance of pleural and pericardial effusion in CA is scarce. Methods Patients with transthyretin (ATTR) and light chain (AL) CA were included in a clinical registry. All patients underwent transthoracic echocardiography at baseline. The presence of pericardial and pleural effusion was determined in every patient. The clinical endpoint was defined as cardiac death or heart failure hospitalization. Results In total, 143 patients were analysed. Of these, 85 patients were diagnosed with ATTR and 58 patients with AL. Twenty-four patients presented with isolated pericardial effusion and 35 with isolated pleural effusion. In 19 patients, both pericardial and pleural effusion were found and in 65 patients no effusion was present at baseline. The presence of pleural effusion correlated well with poor RV function, measured by global RV free-wall strain (p = 0.007) in patients with AL, but not in ATTR. No such correlation could be found for pericardial effusion in either amyloidosis subtype. Patients with AL presenting with pleural effusion had worse outcomes compared to patients with pericardial effusion alone or no effusion at baseline. In the ATTR group, there was no difference in outcomes according to presence and type of effusion. Conclusion More than 50% of patients with CA presented with pleural and/or pericardial effusions. While pleural effusion was clearly associated with poor RV function in AL, we were not able to detect this association with pericardial effusion.

Background In heart failure with preserved ejection fraction (HFpEF), echocardiographic studies suggest that global longitudinal strain (GLS) has an impact on survival. Feature-tracking cardiovascular MRI also allows for strain analysis; however, to the knowledge of the authors, little is known about its prognostic value and whether it reflects severity of diffuse fibrosis, as assessed by cardiovascular MRI T1 mapping. Purpose To investigate the association between myocardial strain at cardiovascular MRI with extracellular volume by T1 mapping and outcome in participants with HFpEF. Materials and Methods In this secondary analysis of a prospective study (NCT03405987), consecutive participants with HFpEF underwent cardiovascular MRI between July 2012 and March 2018, including T1 mapping and three-dimensional strain analysis. Extracellular volume and strain results were assessed to determine if there was a correlation between these two factors. Cox regression was performed to determine the prognostic relevance of MRI-derived myocardial strain for a combined end point (events) of heart failure hospitalizations and cardiovascular death. Results In total, 206 consecutive participants with HFpEF (mean age, 71 years ± 8 [standard deviation]; 69% women) were included. Median myocardial global longitudinal strain (GLS) at MRI was -8.5% and showed low correlation with extracellular volume (r = 0.28; P = .003). A total of 109 events (53%) were recorded during a follow-up of 38 months ± 29. Participants with a GLS above the median had higher event rates (log-rank test, P < .001). By multivariable Cox regression analysis, GLS remained independently associated with outcome (hazard ratio, 1.06 per 1% strain increase; 95% confidence interval: 1.01, 1.11; P = .03) when corrected for risk factors including age, diabetes, renal function, N-terminal pro-b-type natriuretic peptide serum concentration, and right ventricular size and function. Conclusion In participants with heart failure with preserved ejection fraction, global longitudinal strain at cardiovascular MRI was correlated with extracellular volume by T1 mapping and was associated with cardiovascular events. © RSNA, 2020 Online supplemental material is available for this article.

Background Heightened risk of cardiac arrest following physical exertion has been reported. Among patients with an implantable defibrillator, an appropriate shock for sustained ventricular arrhythmia was preceded by a retrospective self-report of engaging in mild-to-moderate physical activity. Previous studies evaluating the relationship between activity and sudden cardiac arrest lacked an objective measure of physical activity and women were often underrepresented. Objective To determine the relationship between physical activity, recorded by accelerometer in a wearable cardioverter-defibrillator (WCD), and sustained ventricular arrhythmia among female patients. Methods A dataset of female adult patients prescribed a WCD for a diagnosis of myocardial infarction or dilated cardiomyopathy was compiled from a commercial database. Curve estimation, to include linear and nonlinear interpolation, was applied to physical activity as a function of time (days before arrhythmia). Results Among women who received an appropriate WCD shock for sustained ventricular arrhythmia (N = 120), a quadratic relationship between time and activity was present prior to shock. Physical activity increased starting at the beginning of the 30-day period up until day -16 (16 days before the ventricular arrhythmia) when activity begins to decline. Conclusion For patients who received treatment for sustained ventricular arrhythmia, a decline in physical activity was found during the 2 weeks preceding the arrhythmic event. Device monitoring for a sustained decline in physical activity may be useful to identify patients at near-term risk of a cardiac arrest.

Aims Concomitant cardiac amyloidosis (CA) in severe aortic stenosis (AS) is difficult to recognize, since both conditions are associated with concentric left ventricular thickening. We aimed to assess type, frequency, screening parameters, and prognostic implications of CA in AS. Methods and results A total of 191 consecutive AS patients (81.2 ± 7.4 years; 50.3% female) scheduled for transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Overall, 81.7% underwent complete assessment including echocardiography with strain analysis, electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), 99mTc‐DPD scintigraphy, serum and urine free light chain measurement, and myocardial biopsy in immunoglobulin light chain (AL)‐CA. Voltage/mass ratio (VMR; Sokolow–Lyon index on ECG/left ventricular mass index) and stroke volume index (SVi) were tested as screening parameters. Receiver operating characteristic curve, binary logistic regression, and Kaplan–Meier curve analyses were performed. CA was found in 8.4% of patients (n = 16); 15 had transthyretin (TTR)‐CA and one AL‐CA. While global longitudinal strain by echo did not reliably differentiate AS from CA‐AS [area under the curve (AUC) 0.643], VMR as well as SVi showed good discriminative power (AUC 0.770 and 0.773, respectively), which was comparable to extracellular volume by CMR (AUC 0.756). Also, VMR and SVi were independently associated with CA by multivariate logistic regression analysis (P = 0.016 and P = 0.027, respectively). CA did not significantly affect survival 15.3 ± 7.9 months after TAVR (P = 0.972). Conclusion Both TTR‐ and AL‐CA can accompany severe AS. Parameters solely based on ECG and echocardiography allow for the identification of the majority of CA‐AS. In the present cohort, CA did not significantly worsen prognosis 15.3 months after TAVR.

Objectives The aim of the present long-term study was to assess the incidence and mode of valve hemodynamic deterioration (VHD) of bioprosthetic aortic valves, as well as associated factors. Background Modern definitions of bioprosthetic valve deterioration recommend the use of echocardiography for the assessment of transprosthetic gradients and valvular regurgitation. Methods A total of 466 consecutive patients (mean age 73.5 ± 7.5 years, 56.0% women) underwent surgical bioprosthetic aortic valve replacement between 1994 and 2014. Clinical assessment, transthoracic echocardiography, and laboratory testing were performed at baseline and follow-up. VHD was defined as mean transprosthetic gradient ≥30 mm Hg and/or at least moderate valvular regurgitation on echocardiography. Patient-prosthesis mismatch was defined as an effective orifice area indexed to body surface area ≤0.8 cm2/m2. Results Patients were followed for a median of 112.3 months (interquartile range: 57.7 to 147.7 months). Among patients with complete follow-up (n = 383), 70 subjects (18.3%; 4.8% per valve-year) developed VHD after a median of 32.4 months (interquartile range: 12.9 to 87.2 months; stenosis, n = 45; regurgitation, n = 16; both, n = 9). Factors associated with VHD by multivariate regression analysis were serum creatinine >2.1 mg/dl (hazard ratio [HR]: 4.143; 95% confidence interval [CI]: 1.740 to 9.866; p = 0.001), porcine tissue valves (HR: 2.241; 95% CI: 1.356 to 3.706; p = 0.002), arterial hypertension (HR: 3.022; 95% CI: 1.424 to 6.410; p = 0.004), and patient-prosthesis mismatch (HR: 1.931; 95% CI: 1.102 to 3.384; p = 0.022). By Kaplan-Meier analysis, elderly subjects showed faster development of VHD (age 80 years, 100.3 months [95% CI: 63.6 to 136.9 months]; p = 0.023). By multivariate Cox regression, age, diabetes, concomitant coronary artery bypass grafting, creatinine, and VHD (p Conclusions On the basis of echocardiography, every fifth patient developed VHD after surgical bioprosthetic heart valve replacement. VHD was associated with renal impairment, the use of porcine tissue valves, arterial hypertension, and patient-prosthesis mismatch. Patients younger than 70 years were not affected by faster VHD.

We aimed to identify cardiopulmonary long-term effects after severe COVID-19 disease as well as predictors of Long-COVID in a prospective registry. A total of 150 consecutive, hospitalized patients (February 2020 and April 2021) were included six months post hospital discharge for a clinical follow-up. Among them, 49% experienced fatigue, 38% exertional dyspnea and 75% fulfilled criteria for Long-COVID. Echocardiography detected reduced global longitudinal strain (GLS) in 11% and diastolic dysfunction in 4%. Magnetic resonance imaging revealed traces of pericardial effusion in 18% and signs of former pericarditis or myocarditis in 4%. Pulmonary function was impaired in 11%. Chest computed tomography identified post-infectious residues in 22%. Whereas fatigue did not correlate with cardiopulmonary abnormalities, exertional dyspnea was associated with impaired pulmonary function (OR 3.6 [95% CI: 1.2–11], p = 0.026), reduced GLS (OR 5.2 [95% CI: 1.6–16.7], p = 0.003) and/or left ventricular diastolic dysfunction (OR 4.2 [95% CI: 1.03–17], p = 0.04). Predictors of Long-COVID included length of in-hospital stay (OR: 1.15 [95% CI: 1.05–1.26], p = 0.004), admission to intensive care unit (OR cannot be computed, p = 0.001) and higher NT-proBNP (OR: 1.5 [95% CI: 1.05–2.14], p = 0.026). Even 6 months after discharge, a majority fulfilled criteria for Long-COVID. While no associations between fatigue and cardiopulmonary abnormalities were found, exertional dyspnea correlated with impaired pulmonary function, reduced GLS and/or diastolic dysfunction.

Background The diagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic value is limited. Purpose The aim of this study was to perform a comprehensive electrophysiological characterization in CA patients and to develop a robust, easy-to-use diagnostic tool. Methods First, we applied electrocardiographic imaging (ECGI) to generate detailed electroanatomical maps in CA patients and controls. Then, a machine learning approach was used to generate a surface ECG-based diagnostic algorithm from the complex dataset. Results Areas of low voltage were localized in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualized in the right ventricle. Potential maps showed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1 to V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in inferior leads II, III, aVF. Ten blinded cardiologists were then asked to identify CA patients by analyzing 12-lead ECGs before and after training for the defined ECG patterns. Training resulted in significant improvements in the detection rate of CA with an AUC of 0.69 before and 0.97 after training (Figure). Conclusion Using a machine learning approach, a robust ECG-based tool was developed to detect CA from detailed electroanatomical mapping of CA patients. The developed tool proved to be a simple and reliable diagnostic tool to suspect CA without the aid of advanced imaging modalities. Funding Acknowledgement Type of funding sources: None.

Background Heart failure with preserved ejection fraction (HFpEF) is the most common form of HF and its prevalence is approaching epidemic proportions. Current treatment strategies aim to improve clinical status and reduce mortality rates. Episodes of acute HF are one of the main reasons for hospitalization in people over 65 years; however, they have not been well studied in HFpEF patients yet. Objectives The aim of this study was to investigate the impact of recurrent HF hospitalizations on long-term outcomes and to find predictors for subsequent events. Methods Between December 2010 and December 2019, 422 patients with confirmed HFpEF were enrolled in this study and prospectively followed. Results During follow-up, 190 HFpEF patients (45%) experienced HF hospitalizations with a median frequency of 2 (IQR: 1–4). Those presenting with acute HF had higher body mass indices (p=0.018), worse performance in 6-minute walking tests (p Conclusions HFpEF patients experiencing recurrent HF hospitalizations have worse long-term outcome. Intensive efforts should be made to maintain HFpEF patients compensated over time. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis

Significant expression of neprilysin (NEP) is found on neutrophils, which present the transmembrane integer form of the enzyme. This study aimed to investigate the relationship of neutrophil transmembrane neprilysin (mNEP) with disease severity, adverse remodeling, and outcome in HFrEF. In total, 228 HFrEF, 30 HFpEF patients, and 43 controls were enrolled. Neutrophil mNEP was measured by flow-cytometry. NEP activity in plasma and blood cells was determined for a subset of HFrEF patients using mass-spectrometry. Heart failure (HF) was characterized by reduced neutrophil mNEP compared to controls (p &lt, 0.01). NEP activity on peripheral blood cells was almost 4-fold higher compared to plasma NEP activity (p = 0.031) and correlated with neutrophil mNEP (p = 0.006). Lower neutrophil mNEP was associated with increasing disease severity and markers of adverse remodeling. Higher neutrophil mNEP was associated with reduced risk for mortality, total cardiovascular hospitalizations, and the composite endpoint of both (p &lt, 0.01 for all). This is the first report describing a significant role of neutrophil mNEP in HFrEF. The biological relevance of neutrophil mNEP and exact effects of angiotensin-converting-enzyme inhibitors (ARNi) at the neutrophil site have to be determined. However, the results may suggest early initiation of ARNi already in less severe HF disease, where effects of NEP inhibition may be more pronounced.

Aims: We tested the hypothesis that artificial intelligence (AI)-powered algorithms applied to cardiac magnetic resonance (CMR) images could be able to detect the potential patterns of cardiac amyloidosis (CA). Readers in CMR centers with a low volume of referrals for the detection of myocardial storage diseases or a low volume of CMRs, in general, may overlook CA. In light of the growing prevalence of the disease and emerging therapeutic options, there is an urgent need to avoid misdiagnoses. Methods and Results: Using CMR data from 502 patients (CA: n = 82), we trained convolutional neural networks (CNNs) to automatically diagnose patients with CA. We compared the diagnostic accuracy of different state-of-the-art deep learning techniques on common CMR imaging protocols in detecting imaging patterns associated with CA. As a result of a 10-fold cross-validated evaluation, the best-performing fine-tuned CNN achieved an average ROC AUC score of 0.96, resulting in a diagnostic accuracy of 94% sensitivity and 90% specificity. Conclusions: Applying AI to CMR to diagnose CA may set a remarkable milestone in an attempt to establish a fully computational diagnostic path for the diagnosis of CA, in order to support the complex diagnostic work-up requiring a profound knowledge of experts from different disciplines.

Aims Tafamidis improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, it is not yet known whether tafamidis affects cardiac amyloid deposition and structural changes in the myocardium. We aimed to determine disease-modifying effects on myocardial amyloid progression and to identify imaging parameters that could be applied for specific therapy monitoring. Methods and results ATTR-CM patients underwent serial cardiac magnetic resonance (CMR) imaging using T1 mapping techniques to derive extracellular volume (ECV). Patients receiving tafamidis 61 mg (n = 35) or 20 mg (n = 15) once daily showed stable measurements at follow-up (FU) {61 mg: 9.0 [interquartile range (IQR) 7.0–11.0] months, 20 mg: 11.0 (IQR 8.0–18.0) months} in left ventricular (LV) ejection fraction (LVEF; 61 mg: 47.6% vs. 47.5%, P = 0.935; 20 mg: 52.4% vs. 52.1%, P = 0.930), LV mass index (LVMI; 61 mg: 110.2 vs. 106.2 g/m2, P = 0.304; 20 mg: 114.5 vs. 115.4 g/m2, P = 0.900), and ECV (61 mg: 47.5% vs. 47.7%, P = 0.861; 20 mg: 56.7% vs. 57.5%, P = 0.759), whereas treatment-naïve ATTR-CM patients (n = 19) had clear signs of disease progression at the end of the observation period [12.0 (IQR 10.0–21.0) months; LVEF: 53.3% vs. 45.7%, P = 0.031; LVMI: 98.9 vs. 106.9 g/m2, P = 0.027; ECV: 49.3% vs. 54.6%, P = 0.023]. Between-group comparison at FU revealed positive effects in tafamidis 61 mg-treated compared to treatment-naïve patients (LVEF: P = 0.035, LVMI: P = 0.036, ECV: P = 0.030), while those treated with 20 mg showed no difference in the above LV measurements when compared with treatment-naïve (P = 0.120, P = 0.287, P = 0.158). However, both treatment groups showed clinically beneficial effects compared to the natural course [61 mg, 6-min walk distance (6-MWD): P = 0.005, N-terminal prohormone of brain natriuretic peptide (NT-proBNP): P = 0.002; 20 mg, 6-MWD: P = 0.023, NT-proBNP: P = 0.003]. Conclusion Tafamidis delays myocardial amyloid progression in ATTR-CM patients, resulting in structural, functional, and clinical benefits compared to the natural course. Serial CMR including measurement of ECV may be appropriate for disease-specific therapy monitoring.

Patients with transthyretin cardiac amyloidosis (TTR CA) suffer from impaired exercise capacity, have a poor quality of life (QoL), and approved treatments are lacking. Stimulators of the soluble guanylate cyclase are promising new pharmaceuticals in the treatment armamentarium of heart failure patients. The aim of the present study was to report on the safety and efficacy of riociguat administration in patients with TTR CA. TTR CA patients received riociguat for 4–6 months within the frames of a national named patient use (NPU) program. Parameters of interest included changes in submaximal exercise capacity, invasive hemodynamic parameters, and QoL. Between March 2012 and June 2017, 86 CA patients were screened for the NPU program, of whom 13 TTR CA patients were eligible for participation. In our study cohort, riociguat had an acceptable tolerability profile. At follow-up, we could detect slight improvements in median 6-min walk distance (396 m [interquartile range (IQR) = 340–518] vs. 400 m [IQR = 350–570], P = 0.045), New York Heart Association class ≥ III (n = 7 [53.9%] vs. n = 0 [0.0%], P = 0.031), cardiac output (4.3 L/min [IQR = 3.9–5.1] vs. 4.5 L/min [IQR = 4.2–5.1], P = 0.022), diastolic pressure gradient (1.0 mmHg [IQR = −1.5–3.0) vs. −1.0 mmHg [IQR = −3.0–1.0], P = 0.049), and QoL (50.0% [IQR = 40.0–58.0] vs. 60.0% [IQR = 50.0–75.0], P = 0.021). Pulmonary arterial pressures were not altered. The present case series of TTR CA patients indicates that riociguat administration was safe and associated with minor clinical as well as hemodynamic improvements.

Aims Increased afterload to the right ventricle (RV) has been shown to induce myocardial fibrosis at the RV insertion points (RVIPs). Such changes can be discrete but potentially detected by cardiac magnetic resonance (CMR) T1-mapping. Whether RVIP fibrosis is associated with prognosis in heart failure with preserved ejection fraction (HFpEF) is unknown. Methods and results We prospectively investigated 167 consecutive HFpEF patients, a population frequently suffering from post-capillary pulmonary hypertension, who underwent CMR including T1-mapping. About 92.8% also underwent right heart catheterization for haemodynamic assessment. Native T1 times were 995 ± 73 ms at the anterior and 1040 ± 90 ms at the inferior RVIP. By Spearman’s rank order testing, RVIP T1 times were significantly correlated with pulmonary artery pressure (mean PAP, r = 0.313 and 0.311 for anterior and inferior RVIP), pulmonary artery wedge pressure (r = 0.301 and 0.251) and right atrial pressure (r = 0.245 and 0.185; P for all Conclusion Interstitial expansion of the anterior RVIP as detected by CMR T1-mapping reflects haemodynamic alterations, and is independently related with prognosis in HFpEF.

The renin-angiotensin system plays an important role in the development and progression of heart failure (HF). In addition to the classical renin-angiotensin pathway, an alternative pathway produces Angs (angiotensins), which counteract the negative effects of Ang II. We hypothesized that Ang profiling could provide insights into the pathogenesis and prognosis of HF with preserved ejection fraction. We aimed to investigate the effects of Angs on outcome in HF with preserved ejection fraction. Consecutive patients were included into a prospective single-center registry. Clinical, laboratory, and imaging parameters were assessed and serum samples were taken at baseline and measured by mass spectroscopy. Serum equilibrium levels were analyzed in regard to the combined clinical end point of cardiovascular death or HF hospitalization. In total, 155 patients were included during a median follow-up time of 22.5 (interquartile range, 4.0–61.0) months, 52 individuals (34%) reached the combined end point. We identified higher levels of Ang 1–7 and Ang 1–5 as predictors for poor outcome. After adjusting for potential confounding factors, Ang 1–5 remained predictive for poor outcome. In addition to Ang 1–7 and Ang 1–5, the novel ACE (angiotensin-converting enzyme) independent Ang composite marker [Ang 1–7+Ang 1–5] was shown to predict adverse events. We conclude that Angs of the alternative renin-angiotensin system seem to play a role in HF with preserved ejection fraction and are linked to outcome in patients with HF and preserved ejection fraction. Ang 1–5 and the alternative renin-angiotensin system composite marker [Ang 1–7+Ang 1–5] are independent predictors of outcome.

Objectives This study investigated the diagnostic and prognostic value of cardiac magnetic resonance (CMR) imaging in chronic aortic regurgitation (AR). Background Accurate quantification of AR severity by echocardiography frequently remains difficult. CMR is recommended as the complementary method; however, its accuracy and prognostic utility remain unknown. Methods A total of 232 consecutive patients (34.5% were females 55.5 ± 19.8 years of age) with chronic AR (including 40 with moderate to severe and 44 with severe AR on echocardiography) underwent CMR within 4 weeks of echocardiography. CMR included phase-contrast velocity-encoded imaging for the measurement of regurgitant volume and fraction at the sinotubular junction and assessment of holodiastolic retrograde flow (HRF) in the descending aorta. Significant AR was defined as the presence of HRF on CMR. Patients were followed prospectively, and multivariate Cox regression was applied for outcome analysis using a combination of heart failure, hospitalization, and cardiovascular death as primary endpoint. Results AR severity on the basis of echo was reclassified in a significant number of patients according to CMR: 6.8% with mild AR on echo had HRF on CMR, whereas 34.1% with severe AR on echo did not have HRF on CMR and were reclassified as having nonsignificant AR. In 40 patients with uncertain AR severity (moderate to severe) on echo, 45.0% had HRF on CMR, indicating severe AR. Patients were followed for 35.3 ± 26.6 months. During that period, 63 patients (27.2%) reached the combined endpoint, including 43 (18.5%) with heart failure hospitalizations and 20 (8.6%) with cardiovascular deaths. By multivariate regression analysis, including clinical as well as imaging parameters, only N-terminal pro–B-type natriuretic peptide concentration (hazard ratio: 2.184 [95% confidence interval: 1.468 to 3.248]; p Conclusions In chronic AR, CMR has the potential to add important diagnostic and prognostic information.

Objectives Decision making in severe aortic stenosis (AS) requires a comprehensive pre-operative evaluation of the risk-to-benefit ratio. The aim of this study was to assess whether certain pre-operative symptoms are associated with outcome after surgical aortic valve replacement (SAVR). Background The cardinal symptoms of AS indicating a need for intervention are angina, symptoms of heart failure, and syncope. Nevertheless, it remains unknown whether the presence of these more advanced symptoms conveys an increased risk after SAVR and whether the detection of early symptoms in patients with asymptomatic AS should be emphasized more in routine clinical practice. Methods A total of 625 patients with isolated severe AS undergoing elective SAVR were prospectively enrolled in this long-term observational study. Results Patients experiencing syncope had significantly smaller left ventricular diameters (p = 0.02), left atrial diameters (p = 0.043), right ventricular diameters (p = 0.04), and right atrial diameters (p = 0.001), smaller aortic valve areas (p = 0.048), and lower indexed stroke volumes (p = 0.043) compared with patients without syncope. Syncope conveyed an increased risk for mortality after SAVR that persisted after multivariate adjustment for a bootstrap-selected confounder model, with an adjusted hazard ratio of 2.27 (95% confidence interval: 1.04 to 4.95; p = 0.04) for 1-year short-term mortality and an adjusted hazard ratio of 2.11 (95% confidence interval: 1.39 to 3.21; p Conclusions This long-term observational study in a large contemporary cohort of patients with AS for the first time demonstrates that syncope represents an underestimated threat in aortic stenosis, associated with poor prognosis after SAVR. Importantly, other primary indications for SAVR (i.e., dyspnea, angina, and decreased left ventricular function) were associated with significantly better post-operative outcomes than syncope. Patients experiencing syncope displayed a specific pathophysiologic phenotype characterized by a smaller aortic valve area, smaller cardiac cavities, and lower stroke volumes.