Comparison of preoperative NT-proBNP and simple cardiac risk scores for predicting postoperative morbidity after non-cardiac surgery with intermediate or high surgical risk.

BACKGROUND: Chronic heart failure (HF) is frequent in elderly patients undergoing non-cardiac surgery. Preoperative risk stratification is vital and can be achieved using simple clinical risk scores or preoperative N-terminal prohormone of brain natriuretic peptide (NT-proBNP) measurement. This study aimed to compare the predictivity of the revised cardiac risk index (RCRI), the American University of Beirut cardiovascular risk index (AUB-HAS2), and a score proposed by Andersson et al. for postoperative 30-day morbidity to preoperative NT-proBNP. METHODS: Preoperative NT-proBNP was measured in 199 consecutive patients aged ≥ 65 years undergoing elective non-cardiac surgery with intermediate or high surgical risk. The areas under the receiver operating characteristic curve (AUCROC) for the composite morbidity endpoint (CME) comprising the incidence of any rehospitalisation, acute decompensated HF, acute kidney injury, and any infection at postoperative day 30 were assessed. Multivariable logistic regression analysis derived new scores from the simple risk scores and the NT-proBNP cut-off of 450 pg/mL. RESULTS: AUB-HAS2, but not RCRI or Andersson score, significantly predicted the CME (AUB-HAS2: AUCROC 0.646, p < 0.001; RCRI: AUCROC 0.560, p = 0.126; Andersson: AUCROC 0.487, p = 0.760). The AUCROC was comparable between preoperative NT-proBNP (0.679, p < 0.001) and AUB-HAS2 (p = 0.334). Multivariable analyses revealed a preoperative NT-proBNP ≥ 450 pg/mL to be the strongest predictor of CME among the individual score components (p < 0.001). Adding preoperative NT-proBNP improved the predictive value of AUB-HAS2 and RCRI (modified AUB-HAS2: AUCROC 0.703, p < 0.001; modified RCRI: AUCROC 0.679, p < 0.001; both p < 0.001 vs original scores). The predictive value of the modified RCRI and AUB-HAS2 was comparable to preoperative NT-proBNP alone (p = 0.988 vs modified RCRI, p = 0.367 vs modified AUB-HAS2). CONCLUSIONS: The predictive value of postoperative morbidity varies significantly between the available simple perioperative risk scores and can be enhanced by preoperative NT-proBNP. New scores, including preoperative NT-proBNP, should be evaluated in large multicentre cohorts. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00027871.

Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.

The aetiology of heart failure with preserved ejection fraction (HFpEF) is heterogenous and overlaps with that of several comorbidities like atrial fibrillation, diabetes mellitus, chronic kidney disease, valvular heart disease, iron deficiency, or sarcopenia. The diagnosis of HFpEF involves evaluating cardiac dysfunction through imaging techniques and assessing increased left ventricular filling pressure, which can be measured directly or estimated through various proxies including natriuretic peptides. To better narrow down the differential diagnosis of HFpEF, European and American heart failure guidelines advocate the use of different algorithms including comorbidities that require diagnosis and rigorous treatment during the evaluation process. Therapeutic recommendations differ between guidelines. Whilst sodium glucose transporter 2 inhibitors have a solid evidence base, the recommendations differ with regard to the use of inhibitors of the renin-angiotensin-aldosterone axis. Unless indicated for specific comorbidities, the use of beta-blockers should be discouraged in HFpEF. The aim of this article is to provide an overview of the current state of the art in HFpEF diagnosis, clinical evaluation, and treatment.

A Novel Rat Model of Mild Pulmonary Hypertension Associated with Pulmonary Venous Congestion Induced by Left Pulmonary Vein Banding.

Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common form of PH. In PH-LHD, changes in the pulmonary vasculature are assumed to be mainly caused by pulmonary venous congestion. However, the underlying mechanisms of this form of PH are poorly understood. We aimed to establish a model of PH associated with pulmonary venous congestion. Wistar-Kyoto rats underwent partial occlusion of the left pulmonary vein to induce pulmonary venous congestion or sham surgery and were assessed at various time points post-surgery (3, 6, 9, 12 weeks). In vivo cardiopulmonary phenotyping was performed by using echocardiography along with heart catheterization. Histomorphometry methods were used to assess pulmonary vascular remodeling (e.g., wall thickness, degree of muscularization). Left pulmonary vein banding (PVB) resulted in mildly elevated right ventricular systolic pressure and moderate right ventricular hypertrophy. In PVB rats, small- and medium-sized pulmonary vessels in the left lung were characterized by increased wall thickness and muscularization. Taken together, our data demonstrate that left PVB-induced pulmonary venous congestion is associated with pulmonary vascular remodeling and mild PH.

Preoperative routine measurement of NT-proBNP predicts postoperative morbidity after non-cardiac surgery with intermediate or high surgical risk: an observational study.

BACKGROUND: Chronic heart failure (HF) is a common clinical condition associated with adverse outcomes in elderly patients undergoing non-cardiac surgery. This study aimed to estimate a clinically applicable NT-proBNP cut-off that predicts postoperative 30-day morbidity in a non-cardiac surgical cohort. METHODS: One hundred ninety-nine consecutive patients older than 65 years undergoing elective non-cardiac surgery with intermediate or high surgical risk were analysed. Preoperative NT-proBNP was measured, and clinical events were assessed up to postoperative day 30. The primary endpoint was the composite morbidity endpoint (CME) consisting of rehospitalisation, acute decompensated heart failure (ADHF), acute kidney injury (AKI), and infection at postoperative day 30. Secondary endpoints included perioperative fluid balance and incidence, duration, and severity of perioperative hypotension. RESULTS: NT-proBNP of 443 pg/ml had the highest accuracy in predicting the composite endpoint; a clinical cut-off of 450 pg/ml was implemented to compare clinical endpoints. Although 35.2% of patients had NT-proBNP above the threshold, only 10.6% had a known history of HF. The primary endpoint was the composite morbidity endpoint (CME) consisting of rehospitalisation, acute decompensated heart failure (ADHF), acute kidney injury (AKI), and infection. Event rates were significantly increased in patients with NT-proBNP > 450 pg/ml (70.7% vs. 32.4%, p < 0.001), which was due to the incidence of cardiac rehospitalisation (4.4% vs. 0%, p = 0.018), ADHF (20.1% vs. 4.0%, p < 0.001), AKI (39.8% vs. 8.3%, p < 0.001), and infection (46.3% vs. 24.4%, p < 0.01). Perioperative fluid balance and perioperative hypotension were comparable between groups. Preoperative NT-proBNP > 450 pg/ml was an independent predictor of the CME in a multivariable Cox regression model (hazard ratio 2.92 [1.72-4.94]). CONCLUSIONS: Patients with NT-proBNP > 450 pg/ml exhibited profoundly increased postoperative morbidity. Further studies should focus on interdisciplinary approaches to improve outcomes through integrated interventions in the perioperative period. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00027871, 17/01/2022.

Twelve-month follow-up results from the SIRONA 2 clinical trial.

AIMS: In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)-guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90 days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12 months. METHODS AND RESULTS: SIRONA 2 is a prospective, multi-centre, open-label, single-arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N-terminal pro-brain natriuretic peptide within 12 months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12 months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9 ± 7.3 mmHg. The device safety profile was excellent with 98.4% freedom from device/system-related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P < 0.0001) and functional capacity as measured by 6 min walk test (P = 0.02) were significantly improved. Patients' adherence to daily transmissions of PAP and vital signs measurements was 95%. CONCLUSIONS: Long-term follow-up of the SIRONA 2 trial supports the safety and accuracy of the Cordella PA Sensor System in enabling comprehensive HF management in NYHA class III HF patients.

Changes in Doppler-Derived Kidney Venous Flow and Adverse Cardiorenal Outcomes in Patients With Heart Failure.

Background The impact of changes in Doppler-derived kidney venous flow in heart failure (HF) is not well studied. We aimed to investigate the association of Doppler-derived kidney venous stasis index (KVSI) and intrakidney venous-flow (IKVF) patterns with adverse cardiorenal outcomes in patients with HF. Methods and Results In this observational cohort study, consecutive inpatients with HF referred to a nephrologist because of a history of diuretic resistance and abnormal kidney function (n=216) underwent spectral kidney assessments after admission (Doppler 1) and 25 to 35 days later (Doppler 2) to identify IKVF patterns (continuous/pulsatile/biphasic/monophasic) and KVSI levels. Cox proportional hazard regression models were used to evaluate the associations between KVSI/IKVF patterns at Doppler 1 as well as changes from Doppler 1 to Doppler 2 and risk of cardiorenal events up to 18 months after admission. Worsening HF or death occurred in 126 patients. Both baseline KVSI (hazard ratio [HR], 1.49 [95% CI, 1.37-1.61] per 0.1-unit increase) and baseline IKVF pattern (HR, 2.47 [95% CI, 2.01-3.04] per 1 pattern severity increase) were significantly associated with worsening HF/death. Increases in both KVSI and IKVF pattern severity from Doppler 1 to 2 were also associated with an increased risk of worsening HF/death (HR, 3.00 [95% CI, 2.08-4.32] per 0.1-unit increase change; and HR, 6.73 [95% CI, 3.27-13.86] per 1 pattern increase in severity change, respectively). Similar results were observed for kidney outcomes. Conclusions Baseline kidney venous flow predicted adverse cardiorenal events, and inclusion of serial kidney venous flow in cardiorenal risk stratification could facilitate clinical decision-making for patients with HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03039959.

[Systemic forms of amyloidosis with cardiac manifestation]. / Systemische Amyloidoseformen mit kardialer Manifestation.

The term amyloidosis summarizes heterogeneous diseases in which a misfolding of protein structures occurs. These misfolded proteins can fundamentally be deposited anywhere in the body and lead to malfunction of the affected organ. There are preferential sites of deposition depending on which protein is misfolded. Cardiac transthyretin (ATTR) amyloidosis is a rare cause of cardiomyopathy and part of an underdiagnosed systemic disease. For cardiac ATTR amyloidosis, which involves deposition of misfolded tranthyretin either as a wild type (wtATTR) or as a mutated form (mATTR or hATTR), evidence-based treatment options have recently become available with slowing of the progression of the cardiomyopathy and a significant reduction of hospitalization rates. Therefore, it is important to diagnose this severe disease at an early stage and to differentiate it from other forms of amyloidosis. A clinical screening is easily possible by determination of free light chains using imaging examinations (cardiac magnetic resonance imaging or scintigraphic procedures) and immunofixation before the definitive diagnosis is made based on a biopsy and/or genetic tests. An interdisciplinary work-up involving hemato-oncology, nephrology, neurology and other disciplines, is indispensable when cardiac amyloidosis is suspected.

Effects of remote haemodynamic-guided heart failure management in patients with different subtypes of pulmonary hypertension: insights from the MEMS-HF study.

AIM: The CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) investigated safety and efficacy of pulmonary artery pressure (PAP)-guided remote patient management (RPM) in New York Heart Association (NYHA) class III outpatients with at least one heart failure hospitalization (HFH) during the previous 12 months. This pre-specified subgroup analysis investigated whether RPM effects depended on presence and subtype of pulmonary hypertension (PH). METHODS AND RESULTS: In 106/234 MEMS-HF participants, Swan-Ganz catheter tracings obtained during sensor implant were available for off-line manual analysis jointly performed by two experts. Patients were classified into subgroups according to current PH definitions. Isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH) were present in 38 and 36 patients, respectively, whereas 31 patients had no PH. Clinical characteristics were comparable between subgroups, but among patients with PH pulmonary vascular resistance was higher (p = 0.029) and pulmonary artery compliance lower (p = 0.003) in patients with CpcPH. During 12 months of PAP-guided RPM, all PAPs declined in IpcPH and CpcPH subgroups (all p < 0.05), whereas only mean and diastolic PAP decreased in patients without PH (both p < 0.05). Improvements in post- versus pre-implant HFH rates were similar in CpcPH (0.639 events/patient-year; hazard ratio [HR] 0.37) and IpcPH (0.72 events/patient-year; HR 0.45) patients. Participants without PH benefited most (0.26 events/patient-year; HR 0.17, p = 0.04 vs. IpcPH/CpcPH patients). Quality of life and NYHA class improved significantly in all subgroups. CONCLUSIONS: Outpatients with NYHA class III symptoms with at least one HFH during 1 year pre-implant benefitted significantly from PAP-guided RPM during post-implant follow-up irrespective of presence or subtype of PH at baseline.

Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series.

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14-39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty® (Pfizer-BioNTech) (n = 11), Vaxzevria® (AstraZenica) (n = 2) and Janssen® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4+ and CD8+ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4+ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.

Safety and efficacy of a wireless pulmonary artery pressure sensor: primary endpoint results of the SIRONA 2 clinical trial.

AIMS: Implantable pulmonary artery pressure (PAP) sensors have been shown to reduce heart failure hospitalizations (HFH) in selected patients. The goal of this study was to evaluate the safety and efficacy of a novel wireless PAP monitoring system in patients with heart failure (HF). METHODS AND RESULTS: This is a prospective, multi-centre, open-label, single-arm trial evaluating the safety and efficacy of the Cordella™ PA Sensor System including the comprehensive Cordella™ Heart Failure System (CHFS) in patients with New York Heart Association (NYHA) Class III heart failure with a heart failure hospitalization and/or increase of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) within 12 months of enrolment. The primary efficacy endpoint was the accuracy of PA sensor mean PAP measurements, compared with fluid-filled catheter mean PAP measurements obtained by standard right heart catheterization (RHC) at 90 days post-implant, assessed in all patients with a successful implant. The primary safety endpoint was freedom from adverse events associated with use of the Cordella PA Sensor System through 30 days post-implant, assessed in all patients who entered the cath lab for PA sensor implant. The PA sensor was successfully implanted in 70 patients. Equivalence between the PA sensor and RHC for mean pulmonary artery pressures was excellent with measurements confined within the equivalence bounds of -4.0 to 4.0 mmHg (mean PAP: 0.0 to 2.9 mmHg, P = 0.003). The device safety profile was excellent with 98.6% freedom from Device System Related Complications, defined as invasive treatment, device explant or death. There were no pressure sensor failures. Patients' adherence to daily measurement transmissions of PAP and vital signs was 94%. CONCLUSIONS: This trial supports the safety and efficacy of the Cordella PA Sensor System and in conjunction with the CHFS enables comprehensive HF management in NYHA class III heart failure patients.

Pulmonary Artery Pressure-Guided Telemonitoring Reduced Pulmonary Artery Pressure but Did Not Result in Higher Doses of Guideline-Directed Medical Therapy-Observations from an Advanced Elderly German Heart Failure Cohort.

Introduction: Remote pulmonary artery pressure (PAP)-guided heart failure (HF) therapy for NYHA class III patients has been shown to reduce hospitalizations and increase survival. We aimed to assess whether PAP monitoring allows for the increase in HF directed medication in an elderly German cohort of advanced HF patients already receiving clinically optimized HF medication. Methods: We analyzed PAP and HF medication dosage, including diuretics, in 24 patients (mean age, 76 years) using implanted PAP-sensors during the first 12 months of PAP-guided HF care in an interdisciplinary HF unit. Results: During 12 months of PAP-guided HF therapy, PAP decreased significantly (△PAP systolic−6 ± 10, △PAP diastolic−4 ± 7, △PAP mean−4 ± 8 mm Hg, p < 0.01 for all). 16% of patients had an unplanned HF hospitalization. There was no significant change over time with respect to the dosage of RAAS inhibitors (ACE-I/ARB/ARNI), Beta blockers, or MRA treatments. In contrast, the dosage of loop diuretics increased significantly (2.1 ± 0.5-fold) over time. In the comparison of a "responder" (patients with PAP and diuretic dose decline) and "non-responder" (patients with PAP and diuretic dose increase) group, there were no significant differences between any of the baseline, medication, or HF hospitalization characteristics between the two groups. Conclusions: In elderly patients treated with clinically optimized HF medication, no further evidence-based medication increase could be achieved using PAP-guided HF care. However, by individual adjustment of diuretic dosage, a significant decline in PAP over time occurred, which could not be predicted by any of the baseline characteristics.

Pulmonary artery sensor system pressure monitoring to improve heart failure outcomes (PASSPORT-HF): rationale and design of the PASSPORT-HF multicenter randomized clinical trial.

BACKGROUND: Remote monitoring of patients with New York Heart Association (NYHA) functional class III heart failure (HF) using daily transmission of pulmonary artery (PA) pressure values has shown a reduction in HF-related hospitalizations and improved quality of life in patients. OBJECTIVES: PASSPORT-HF is a prospective, randomized, open, multicenter trial evaluating the effects of a hemodynamic-guided, HF nurse-led care approach using the CardioMEMS™ HF-System on clinical end points. METHODS AND RESULTS: The PASSPORT-HF trial has been commissioned by the German Federal Joint Committee (G-BA) to ascertain the efficacy of PA pressure-guided remote care in the German health-care system. PASSPORT-HF includes adult HF patients in NYHA functional class III, who experienced an HF-related hospitalization within the last 12 months. Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy. Patients will be randomized centrally 1:1 to implantation of a CardioMEMS™ sensor or control. All patients will receive post-discharge support facilitated by trained HF nurses providing structured telephone-based care. The trial will enroll 554 patients at about 50 study sites. The primary end point is a composite of the number of unplanned HF-related rehospitalizations or all-cause death after 12 months of follow-up, and all events will be adjudicated centrally. Secondary end points include device/system-related complications, components of the primary end point, days alive and out of hospital, disease-specific and generic health-related quality of life including their sub-scales, and laboratory parameters of organ damage and disease progression. CONCLUSIONS: PASSPORT-HF will define the efficacy of implementing hemodynamic monitoring as a novel disease management tool in routine outpatient care. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04398654, 13-MAY-2020.

[Novel European Heart Failure Guidelines - Change in Treatment Paradigms]. / Neue europäische Herzinsuffizienz-Leitlinie 2021 ­ Paradigmenwechsel in der Therapie.

NEW DRUG THERAPY ALGORITHM FOR HEART FAILURE WITH LVEF ≤ 40 %: The new Heart Failure Guidelines 2021 recommend a fundamentally new treatment algorithm for heart failure (HF) with reduced ejection fraction ≤ 40 % (HFrEF). This involves, that all four mortality reducing substances (ARNI or ACE-Inhibitor, Betablocker, MRA und SGLT-2-Inhibitor) are given as fast as possible. The conventional sequence with stepwise uptitration is no longer recommended. RECOMMENDATIONS FOR HFPEF: The diagnostic algorithm has been simplified for HFpEF, which requires not only signs and symptoms of HF, but also a LVEF ≥ 50 % and additionally objective criteria for a structural and/or functional abnormalities with diastolic dysfunction, elevated filling pressures and elevated natriuretic peptides. Etiology of HFpEF should be evaluated. There is no change in the treatment recommendations of HFpEF in contrast to 2016, but a short-term revision of the guidelines can be expected. IMPORTANCE OF SELECTED CONCOMITANT DISEASES: The primary recommendation for atrial fibrillation is anticoagulation with NOAKs. The value of PVI has been upgraded. The decision for transcatheter therapy of secondary mitral regurgitation should be made in the heart team if appropriate criteria are present. ADVANCED HEART FAILURE: For the diagnosis of advanced heart failure four key criteria were defined, including severe and persistent symptoms (NYHA III or IV), a severe cardiac dysfunction, episodes of congestion treated with i. v. diuretics and/or inotropes, malignant arrhythmias and a severe impairment of exercise capacity. There is a new treatment algorithm for these patients, in which the importance of mechanical support was upgraded. ACUTE HEART FAILURE: For patients with acute heart failure, integration into a disease management program and a multimodal, multiprofessional therapy concept is recommended after discharge from inpatient treatment.

Less loop diuretic use in patients on sacubitril/valsartan undergoing remote pulmonary artery pressure monitoring.

AIMS: Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). METHODS AND RESULTS: The MEMS-HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS-HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2 ] vs. non-users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2 , P = 0.0002, P < 0.0001, and P = 0.0015, respectively). In contrast, mean pulmonary artery pressure (PAP) values were comparable between groups (29 ± 11 vs. 31 ± 11 mmHg, P = 0.127). Utilization of loop diuretics was lower in patients taking sacubitril/valsartan compared with those without (P = 0.01). Significant predictor of loop diuretic use was a history of renal failure (P = 0.005) but not age (P = 0.091). After subjects were stratified by sacubitril/valsartan or other diuretic use, PAP was nominally, but not significantly lower in sacubitril/valsartan-treated patients (baseline: P = 0.52; 6 months: P = 0.07; 12 months: P = 0.53), while there was no difference in outcome or PAP changes. This difference was observed despite lower CI (P = 0.0015). Comparable changes were not observed for other non-loop diuretics (P = 0.21). CONCLUSIONS: In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes.

Hereditary transthyretin-related amyloidosis is frequent in polyneuropathy and cardiomyopathy of no obvious aetiology.

BACKGROUND: Hereditary Transthyretin-Related Amyloidosis, a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene, is characterized by the deposition of insoluble misfolded protein fibrils. The diagnosis, especially in non-endemic areas, is typically delayed by 4-5 years; a misdiagnosis due to clinical heterogeneity is common. The study objective was to define the prevalence of Hereditary Transthyretin-Related Amyloidosis in patients with polyneuropathy and/or cardiomyopathy of no obvious aetiology. METHOD: A multicenter observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis"-TRAM study was performed in Germany, Austria, and Switzerland. RESULTS: A total of 5141 participants were recruited by 50 neurologic and 27 cardiologic specialized centres. Genetic analysis demonstrated a 1.1% Hereditary Transthyretin-Related Amyloidosis positivity rate among patients with polyneuropathy and/or cardiomyopathy of not obvious aetiology. Twenty-one various TTR variants (TTR-positive) were identified. Body Mass Index was lower in the TTR-positive patients as an indicator for the involvement of the autonomic nervous system; the age of onset of clinical manifestations was higher in TTR-positive patients. There were no other genotype-phenotype correlations or the prevalence of specific clinical manifestations in TTR-positive patients. CONCLUSIONS: Our data support the fact that Hereditary Transthyretin-Related Amyloidosis is underdiagnosed in polyneuropathy and cardiomyopathy patients. Routine implementation of genetic testing is recommended in patients with unexplained polyneuropathy and/or cardiomyopathy to accelerate the earlier diagnosis and the time-sensitive treatment initiation.KEY MESSAGESMore than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis" TRAM study and screened for pathogenic TTR variants.The study demonstrated >1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic TTR variant.Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation.

Novel Therapeutic Targets for the Treatment of Right Ventricular Remodeling: Insights from the Pulmonary Artery Banding Model.

Right ventricular (RV) function is the main determinant of the outcome of patients with pulmonary hypertension (PH). RV dysfunction develops gradually and worsens progressively over the course of PH, resulting in RV failure and premature death. Currently, approved therapies for the treatment of left ventricular failure are not established for the RV. Furthermore, the direct effects of specific vasoactive drugs for treatment of pulmonary arterial hypertension (PAH, Group 1 of PH) on RV are not fully investigated. Pulmonary artery banding (PAB) allows to study the pathogenesis of RV failure solely, thereby testing potential therapies independently of pulmonary vascular changes. This review aims to discuss recent studies of the mechanisms of RV remodeling and RV-directed therapies based on the PAB model.

Post-myocardial infarction heart failure dysregulates the bone vascular niche.

The regulation of bone vasculature by chronic diseases, such as heart failure is unknown. Here, we describe the effects of myocardial infarction and post-infarction heart failure on the bone vascular cell composition. We demonstrate an age-independent loss of type H endothelium in heart failure after myocardial infarction in both mice and humans. Using single-cell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium, showing increased expression of inflammatory genes, including IL1B and MYC, in ischemic heart failure. Endothelial-specific overexpression of MYC was sufficient to induce type H bone endothelial cells, whereas inhibition of NLRP3-dependent IL-1ß production partially prevented the post-myocardial infarction loss of type H vasculature in mice. These results provide a rationale for using anti-inflammatory therapies to prevent or reverse the deterioration of bone vascular function in ischemic heart disease.