Characteristics, treatment, and outcomes of early vs. late enrollees of the STRONG-HF trial.

BACKGROUND: The STRONG-HF trial showed that high-intensity care (HIC) consisting of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up reduced all-cause death or heart failure (HF) readmission at 180 days compared to usual care (UC). We hypothesized that significant differences in patient characteristics, management, and outcomes over the enrolment period may exist. METHODS: Two groups of the 1,078 patients enrolled in STRONG-HF were created according to the order of enrolment within center. The early group consisted of the first 10 patients enrolled at each center (N = 342) and the late group consisted of the following patients (N = 736). RESULTS: Late enrollees were younger, had more frequently reduced ejection fraction, slightly lower NT-proBNP and creatinine levels compared with early enrollees. The primary outcome occurred less frequently in early compared to late enrollees (15% vs. 21%, aHR 0.65, 95% CI 0.42-0.99, P = .044). No treatment-by-enrolment interaction was seen in respect to the average percentage of optimal dose of GDMT after randomization, which was consistently higher in early and late patients randomized to HIC compared to UC. The higher use of renin-angiotensin-inhibitors in the HIC arm was more pronounced in the late enrollees both after randomization (interaction-P = .013) and at 90 days (interaction-P < .001). No interaction was observed for safety events. Patients randomized late to UC displayed a trend toward more severe outcomes (26% vs. 16%, P = .10), but the efficacy of HIC showed no interaction with the enrolment group (aHR 0.77, 95% CI 0.35-1.67 in early and 0.58, 95% CI 0.40-0.83 in late enrollees, adjusted interaction-P = .51) with similar outcomes in the HIC arm in late and early enrollees (16% vs. 13%, P = .73). CONCLUSIONS: Late enrollees have different clinical characteristics and higher event rates compared to early enrollees. GDMT implementation in the HIC arm robustly achieved similar doses with consistent efficacy in early and late enrollees, mitigating the higher risk of adverse outcome in late enrollees. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03412201.

Safety Indicators in Patients Receiving High-intensity Care After Hospital Admission for Acute Heart Failure: The STRONG-HF Trial.

BACKGROUND: Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) demonstrated the safety and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) with high-intensity care (HIC) compared with usual care in patients hospitalized for acute heart failure (HF). In the HIC group, the following safety indicators were used to guide up-titration: estimated glomerular filtration rate of <30 mL/min/1.73 m2, serum potassium of >5.0 mmol/L, systolic blood pressure (SBP) of <95 mmHg, heart rate of <55 bpm, and N-terminal pro-B-type natriuretic peptide concentration of >10% higher than predischarge values. METHODS AND RESULTS: We examined the impact of protocol-specified safety indicators on achieved dose of GDMT and clinical outcomes. Three hundred thirteen of the 542 patients in the HIC arm (57.7%) met ≥1 safety indicator at any follow-up visit 1-6 weeks after discharge. As compared with those without, patients meeting ≥1 safety indicator had more severe HF symptoms, lower SBP, and higher heart rate at baseline and achieved a lower average percentage of GDMT optimal doses (mean difference vs the HIC arm patients not reaching any safety indicator, -11.0% [95% confidence interval [CI] -13.6 to -8.4%], P < .001). The primary end point of 180-day all-cause death or HF readmission occurred in 15.0% of patients with any safety indicator vs 14.2% of those without (adjusted hazard ratio 0.84, 95% CI 0.48-1.46, P = .540). None of each of the safety indicators, considered alone, was significantly associated with the primary end point, but an SBP of <95 mm Hg was associated with a trend toward increased 180-day all-cause mortality (adjusted hazard ratio 2.68, 95% CI 0.94-7.64, P = .065) and estimated glomerular filtration rate decreased to <30 mL/min/1.73 m2 with more HF readmissions (adjusted hazard ratio 3.60, 95% CI 1.22-10.60, P = .0203). The occurrence of a safety indicator was associated with a smaller 90-day improvement in the EURO-QoL 5-Dimension visual analog scale (adjusted mean difference -3.32 points, 95% CI -5.97 to -0.66, P = .015). CONCLUSIONS: Among patients with acute HF enrolled in STRONG-HF in the HIC arm, the occurrence of any safety indicator was associated with the administration of slightly lower GDMT doses and less improvement in quality of life, but with no significant increase in the primary outcome of 180-day HF readmission or death when appropriately addressed according to the study protocol.

NT-proBNP and high intensity care for acute heart failure: the STRONG-HF trial.

AIMS: STRONG-HF showed that rapid up-titration of guideline-recommended medical therapy (GRMT), in a high intensity care (HIC) strategy, was associated with better outcomes compared with usual care. The aim of this study was to assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and its changes early during up-titration. METHODS AND RESULTS: A total of 1077 patients hospitalized for acute heart failure (HF) and with a >10% NT-proBNP decrease from screening (i.e. admission) to randomization (i.e. pre-discharge), were included. Patients in HIC were stratified by further NT-proBNP changes, from randomization to 1 week later, as decreased (≥30%), stable (<30% decrease to ≤10% increase), or increased (>10%). The primary endpoint was 180-day HF readmission or death. The effect of HIC vs. usual care was independent of baseline NT-proBNP. Patients in the HIC group with stable or increased NT-proBNP were older, with more severe acute HF and worse renal and liver function. Per protocol, patients with increased NT-proBNP received more diuretics and were up-titrated more slowly during the first weeks after discharge. However, by 6 months, they reached 70.4% optimal GRMT doses, compared with 80.3% for those with NT-proBNP decrease. As a result, the primary endpoint at 60 and 90 days occurred in 8.3% and 11.1% of patients with increased NT-proBNP vs. 2.2% and 4.0% in those with decreased NT-proBNP (P = 0.039 and P = 0.045, respectively). However, no difference in outcome was found at 180 days (13.5% vs. 13.2%; P = 0.93). CONCLUSION: Among patients with acute HF enrolled in STRONG-HF, HIC reduced 180-day HF readmission or death regardless of baseline NT-proBNP. GRMT up-titration early post-discharge, utilizing increased NT-proBNP as guidance to increase diuretic therapy and reduce the GRMT up-titration rate, resulted in the same 180-day outcomes regardless of early post-discharge NT-proBNP change.

Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial.

BACKGROUND: There is a paucity of evidence for dose and pace of up-titration of guideline-directed medical therapies after admission to hospital for acute heart failure. METHODS: In this multinational, open-label, randomised, parallel-group trial (STRONG-HF), patients aged 18-85 years admitted to hospital with acute heart failure, not treated with full doses of guideline-directed drug treatment, were recruited from 87 hospitals in 14 countries. Before discharge, eligible patients were randomly assigned (1:1), stratified by left ventricular ejection fraction (≤40% vs >40%) and country, with blocks of size 30 within strata and randomly ordered sub-blocks of 2, 4, and 6, to either usual care or high-intensity care. Usual care followed usual local practice, and high-intensity care involved the up-titration of treatments to 100% of recommended doses within 2 weeks of discharge and four scheduled outpatient visits over the 2 months after discharge that closely monitored clinical status, laboratory values, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations. The primary endpoint was 180-day readmission to hospital due to heart failure or all-cause death. Efficacy and safety were assessed in the intention-to-treat (ITT) population (ie, all patients validly randomly assigned to treatment). The primary endpoint was assessed in all patients enrolled at hospitals that followed up patients to day 180. Because of a protocol amendment to the primary endpoint, the results of patients enrolled on or before this amendment were down-weighted. This study is registered with ClinicalTrials.gov, NCT03412201, and is now complete. FINDINGS: Between May 10, 2018, and Sept 23, 2022, 1641 patients were screened and 1078 were successfully randomly assigned to high-intensity care (n=542) or usual care (n=536; ITT population). Mean age was 63·0 years (SD 13·6), 416 (39%) of 1078 patients were female, 662 (61%) were male, 832 (77%) were White or Caucasian, 230 (21%) were Black, 12 (1%) were other races, one (<1%) was Native American, and one (<1%) was Pacific Islander (two [<1%] had missing data on race). The study was stopped early per the data and safety monitoring board's recommendation because of greater than expected between-group differences. As of data cutoff (Oct 13, 2022), by day 90, a higher proportion of patients in the high-intensity care group had been up-titrated to full doses of prescribed drugs (renin-angiotensin blockers 278 [55%] of 505 vs 11 [2%] of 497; ß blockers 249 [49%] vs 20 [4%]; and mineralocorticoid receptor antagonists 423 [84%] vs 231 [46%]). By day 90, blood pressure, pulse, New York Heart Association class, bodyweight, and NT-proBNP concentration had decreased more in the high-intensity care group than in the usual care group. Heart failure readmission or all-cause death up to day 180 occurred in 74 (15·2% down-weighted adjusted Kaplan-Meier estimate) of 506 patients in the high-intensity care group and 109 (23·3%) of 502 patients in the usual care group (adjusted risk difference 8·1% [95% CI 2·9-13·2]; p=0·0021; risk ratio 0·66 [95% CI 0·50-0·86]). More adverse events by 90 days occurred in the high-intensity care group (223 [41%] of 542) than in the usual care group (158 [29%] of 536) but similar incidences of serious adverse events (88 [16%] vs 92 [17%]) and fatal adverse events (25 [5%] vs 32 [6%]) were reported in each group. INTERPRETATION: An intensive treatment strategy of rapid up-titration of guideline-directed medication and close follow-up after an acute heart failure admission was readily accepted by patients because it reduced symptoms, improved quality of life, and reduced the risk of 180-day all-cause death or heart failure readmission compared with usual care. FUNDING: Roche Diagnostics.

The effect of exercise training and physiotherapy on left and right heart function in heart failure with preserved ejection fraction: a systematic literature review.

The impact of exercise training and physiotherapy on heart function and pulmonary circulation parameters in heart failure with preserved ejection fraction (HFpEF) patients is uncertain. Hence, we performed a systematic review of published trials studying physical training in HFpEF population, with a focus on exercise and physiotherapy effect on left ventricular (LV), right ventricular (RV) morphological, functional, and pulmonary circulation parameters. We searched Cochrane Library and MEDLINE/PubMed for trials that evaluated the effect of exercise training and/or physiotherapy in adult HFpEF patients (defined as LVEF ≥ 45%), including publications until March 2021. Our systematic review identified eighteen articles (n = 418 trained subjects, 4 to 52 weeks of training) and covered heterogeneous trials with various populations, designs, methodologies, and interventions. Five of twelve trials revealed a significant reduction of mitral E/e' ratio after the training (- 1.2 to - 4.9). Seven studies examined left atrial volume index; three of them showed its decrease (- 3.7 to - 8 ml/m2). Findings were inconsistent regarding improvement of cardiac output, E/A ratio, and E wave DecT and uncertain for RV function and pulmonary hypertension parameters. For now, no reliable evidence about rehabilitation effect on HFpEF cardiac mechanisms is available. There are some hypotheses generating findings on potential positive effects to parameters of LV filling pressure (E/e'), left atrium size, cardiac output, and RV function. This encourages a broader and more complex assessment of parameters reflecting cardiac function in future HFpEF exercise training studies.

Effect of home-based prehabilitation on postoperative complications after surgery for gastric cancer: randomized clinical trial.

BACKGROUND: Recent studies have demonstrated that prehabilitation improves patients' physical fitness but its impact on postoperative morbidity remains unclear. This study aimed to assess the effect of personalized, multimodal, semisupervised, home-based prehabilitation on postoperative complications after surgery for gastric cancer. METHODS: This RCT was conducted at two centres in Lithuania. Patients (aged at least18 years) with gastric cancer scheduled to undergo elective primary surgery or surgery after neoadjuvant chemotherapy for gastric cancer were randomized (1 : 1) to prehabilitation or standard care. Prehabilitation included exercise interventions focused on endurance, respiratory muscle strength, stretching, and resistance training as well as nutritional and psychological support. The primary outcome was the proportion of patients with postoperative complications within 90 days after surgery. Secondary outcomes included 90-day mortality rate, physical condition, fitness level, nutritional status, quality of life, anxiety and depression level, and proportion of patients completing neoadjuvant chemotherapy. RESULTS: Between February 2020 and September 2022, 128 participants were randomized to prehabilitation (64) or standard care (64), and 122 (prehabilitation 61, control 61) were analysed. The prehabilitation group had increased physical capacity before the operation compared with baseline (mean 6-min walk test change +31 (95 per cent c.i. 14 to 48) m; P = 0.001). The prehabilitation group had a decreased rate of non-compliance with neoadjuvant treatment (risk ratio (RR) 0.20, 95 per cent c.i. 0.20 to 0.56), a 60 per cent reduction in the number of patients with postoperative complications at 90 days after surgery (RR 0.40, 0.24 to 0.66), and improved quality of life compared with the control group. CONCLUSION: Prehabilitation reduced morbidity in patients who underwent gastrectomy for gastric cancer. REGISTRATION NUMBER: NCT04223401 (http://www.clinicaltrials.gov).

Stress Echo 2030: the new ABCDE protocol defining the future of cardiac imaging.

Functional testing with stress echocardiography is based on the detection of regional wall motion abnormality with two-dimensional echocardiography and is embedded in clinical guidelines. Yet, it under-uses the unique versatility of the technique, ideally suited to describe the different functional abnormalities underlying the same wall motion response during stress. Five parameters converge conceptually and methodologically in the state-of-the-art ABCDE protocol, assessing multiple vulnerabilities of the ischemic patient. The five steps of the ABCDE protocol are (1) step A: regional wall motion; (2) step B: B-lines by lung ultrasound assessing extravascular lung water; (3) step C: left ventricular contractile reserve by volumetric two-dimensional echocardiography; (4) step D: coronary flow velocity reserve in mid-distal left anterior descending coronary with pulsed-wave Doppler; and (5) step E: assessment of heart rate reserve with a one-lead electrocardiogram. ABCDE stress echo offers insight into five functional reserves: epicardial flow (A); diastolic (B), contractile (C), coronary microcirculatory (D), and chronotropic reserve (E). The new format is more comprehensive and allows better functional characterization, risk stratification, and personalized tailoring of therapy. ABCDE protocol is an 'ecumenic' and 'omnivorous' functional test, suitable for all stresses and all patients also beyond coronary artery disease. It fits the need for sustainability of the current era in healthcare, since it requires universally available technology, and is low-cost, radiation-free, and nearly carbon-neutral.

Ivabradine for the Prevention of Anthracycline-Induced Cardiotoxicity in Female Patients with Primarily Breast Cancer: A Prospective, Randomized, Open-Label Clinical Trial.

Background and Objectives: Cancer therapy containing anthracyclines is associated with cancer-treatment-related cardiac dysfunction and heart failure (HF). Conventional cardioprotective medications can be frequently complicated by their blood-pressure-lowering effect. Recently, elevated resting heart rate was shown to independently predict mortality in patients with cancer. As a heart rate-lowering drug without affecting blood pressure, ivabradine could present an alternative management of anthracyclines-induced cardiotoxicity. Materials and Methods: This study aimed to investigate the probable protective effects of ivabradine in cancer patients with elevated heart rate (>75 beats per minute) undergoing anthracycline chemotherapy. Patients referred by oncologists for baseline cardiovascular risk stratification before anthracycline chemotherapy who met the inclusion criteria and had no exclusion criteria were randomly assigned to one of two strategies: ivabradine 5 mg twice a day (intervention group) or controls. Electrocardiogram, transthoracic echocardiogram with global longitudinal strain (GLS), troponin I (Tn I), and N-terminal natriuretic pro-peptide (NT-proBNP) were performed at baseline, after two and four cycles of chemotherapy and at six months of follow-up. The primary endpoint was the prevention of a >15% reduction in GLS. Secondary endpoints were effects of ivabradine on Tn I, NT-proBNP, left ventricular (LV) systolic and diastolic dysfunction, right ventricle dysfunction, and myocardial work indices. Results: A total of 48 patients were enrolled in the study; 21 were randomly assigned to the ivabradine group and 27 to the control group. Reduced GLS was detected 2.9 times less often in patients receiving ivabradine than in the control group, but this change was non-significant (OR [95% CI] = 2.9 [0.544, 16.274], p = 0.208). The incidence of troponin I elevation was four times higher in the control group (OR [95% CI] = 4.0 [1.136, 14.085], p = 0.031). There was no significant change in NT-proBNP between groups, but the increase in NT-proBNP was almost 12% higher in the control group (OR [95% CI] = 1.117 [0.347, 3.594], p = 0.853). LV diastolic dysfunction was found 2.7 times more frequently in the controls (OR [95% CI] = 2.71 [0.49, 15.10], p = 0.254). Patients in the ivabradine group were less likely to be diagnosed with mild asymptomatic CTRCD during the study (p = 0.045). No differences in right ventricle function were noted. A significant difference was found between the groups in global constructive work and global work index at six months in favour of the ivabradine group (p = 0.014 and p = 0.025). Ivabradine had no adverse effects on intracardiac conduction, ventricular repolarization, or blood pressure. However, visual side effects (phosphenes) were reported in 14.3% of patients. Conclusions: Ivabradine is a safe, well-tolerated drug that has shown possible cardioprotective properties reducing the incidence of mild asymptomatic cancer-therapy-induced cardiac dysfunction, characterised by a new rise in troponin concentrations and diminished myocardial performance in anthracycline-treated women with breast cancer and increased heart rate. However, more extensive multicentre trials are needed to provide more robust evidence.

Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

BACKGROUND: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. METHODS: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. RESULTS: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (P=0.46) or ISCHEMIA stress echocardiography participants (P=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). CONCLUSIONS: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.

The Experience, Prerequisites, and the Barriers in Organizing a Specialized Rehabilitation Program for Patients with Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a severe progressive disease, associated with reduced exercise capacity and poor quality of life. Although scientific evidence supports the incorporation of specialized training in the treatment of PH, it is only available in a few countries. OBJECTIVES AND METHODS: This article aims to share the experience of implementing a PH rehabilitation program, to summarize the barriers and prerequisites for launching this service, and to assess its early effect. We retrospectively analyzed our pathway in organizing this program, by singling out essential steps. RESULTS: The preparation phase took about 14 months. Establishing and running of a PH rehabilitation program required dedicated rehabilitation specialists to join the multidisciplinary PH expert team. Team members needed to gain special knowledge on exercise training in severely compromised patients; thus, supervision and education by experienced consultants was crucial. The main eligibility criteria for patients were stable status, optimal medical treatment, and motivation to undergo the training. The first results evaluating the effect of a specialized PH training program in 9 patients are promising. Seven of them improved their functional capacity over the period of 15 weeks. CONCLUSIONS: Despite a number of challenges and barriers, the implementation of a specialized rehabilitation program should be encouraged in a few dedicated PH expert centers per country, who are capable to fulfill all prerequisites and organizational aspects. Local PH experts, supervision by an experienced center, in-patient rehabilitation facilities, dedicated personnel, equipment, and patient motivation are essential.

Effect of Supervised Training Therapy on Pulmonary Arterial Compliance and Stroke Volume in Severe Pulmonary Arterial Hypertension and Inoperable or Persistent Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Pulmonary arterial compliance (PAC) is a prognostic parameter in pulmonary arterial hypertension (PAH) reflecting the elasticity of the pulmonary vessels. OBJECTIVES: The objective of this post hoc analysis of a prospective randomized controlled trial (RCT) was to assess the effect of exercise training on PAC and stroke volume (SV) in patients with PAH and persistent/inoperable chronic thromboembolic pulmonary hypertension (CTEPH). METHOD: From the previous RCT, 43 out of 87 patients with severe PAH (n = 29) and CTEPH (n = 14) had complete haemodynamic examinations at baseline and after 15 weeks by right heart catheterization and were analysed (53% female, 79% World Health Organization functional class III/IV, 58% combination therapy, 42% on supplemental oxygen therapy, training group n = 24, and control group n = 19). Medication remained unchanged for all patients. RESULTS: Low-dose exercise training at 4-7 days/week significantly improved PAC (training group 0.33 ± 0.65 mL/mm Hg vs. control group -0.06 ± 1.10 mL/mm Hg; mean difference 0.39 mL/mm Hg, 95% confidence interval [CI] 0.15-0.94 mL/mm Hg; p = 0.004) and SV (training group 9.9 ± 13.4 mL/min vs. control group -4.2 ± 11.0 mL/min; mean difference 14.2 mL, 95% CI 6.5-21.8 mL; p < 0.001) in the training versus control group. Furthermore, exercise training significantly improved cardiac output and pulmonary vascular resistance at rest, peak oxygen consumption, and oxygen pulse. CONCLUSIONS: Our findings suggest that supervised exercise training may improve right ventricular function and PAC at the same time. Further prospective studies are needed to evaluate these findings.

Left ventricular global longitudinal strain predicts elevated cardiac pressures and poor clinical outcomes in patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Risk stratification in patients with non-ischemic dilated cardiomyopathy (NI-DCM) is essential to treatment planning. Global longitudinal strain (GLS) predicts poor prognosis in various cardiac diseases, but it has not been evaluated in a cohort of exclusively NI-DCM. Although deformation parameters have been shown to reflect diastolic function, their association with other hemodynamic parameters needs further elucidation. We aimed to evaluate the association between GLS and E/GLS and invasive hemodynamic parameters and assess the prognostic value of GLS and E/GLS in a prospective well-defined pure NI-DCM cohort. METHODS AND RESULTS: Forty-one patients with NI-DCM were enrolled in the study. They underwent a standard diagnostic workup, including transthoracic echocardiography and right heart catheterization. During a five-year follow-up, 20 (49%) patients reached the composite outcome measure: LV assist device implantation, heart transplantation, or cardiovascular death. Pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure, pulmonary vascular resistance (PVR) correlated with GLS and E/GLS (p < 0.05). ROC analysis revealed that GLS and E/GLS could identify elevated PCWP (≥ 15 mmHg) and PVR (> 3 Wood units). Survival analysis showed GLS and E/GLS to be associated with short- and long-term adverse cardiac events (p < 0.05). GLS values above thresholds of -5.34% and -5.96% indicated 18- and 12-fold higher risk of poor clinical outcomes at one and five years, respectively. Multivariate Cox regression analysis revealed that GLS is an independent long-term outcome predictor. CONCLUSION: GLS and E/GLS correlate with invasive hemodynamics parameters and identify patients with elevated PCWP and high PVR. GLS and E/GLS predict short- and long-term adverse cardiac events in patients with NI-DCM. Worsening GLS is associated with incremental risk of long-term adverse cardiac events and might be used to identify high-risk patients.

The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions.

AIMS: Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world. METHODS AND RESULTS: We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79-0.94), P < 0.001 after adjustment]. This was mostly driven by northeast Asia [n = 9135, HR 0.76 (0.67-0.87), P < 0.001], while no significant differences were seen in other countries. In the OPTIMIZE-HF registry, women also had a lower risk of 1-year death [HR 0.93 (0.89-0.97), P < 0.001]. In the GREAT registry, women were less often prescribed with a combination of angiotensin-converting enzyme inhibitors and beta-blockers at discharge (50% vs. 57%, P = 0.001). CONCLUSION: Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF.

Increase of Myocardial Ischemia Time and Short-Term Prognosis of Patients with Acute Myocardial Infarction during the First COVID-19 Pandemic Wave.

Background and objectives: early reports showed a decrease in admission rates and an increase in mortality of patients with acute myocardial infarction (AMI) during the first wave of COVID-19 pandemic. We sought to investigate whether the COVID-19 pandemic and associated lockdown had an impact on the ischemia time and prognosis of patients suffering from AMI in the settings of low COVID-19 burden. Materials and Methods: we conducted a retrospective data analysis from a tertiary center in Lithuania of 818 patients with AMI. Data were collected from 1 March to 30 June in 2020 during the peri-lockdown period (2020 group; n = 278) and compared to the same period last year (2019 group; n = 326). The primary study endpoint was all-cause mortality during 3 months of follow-up. Secondary endpoints were heart failure severity (Killip class) on admission and ischemia time in patients with acute ST segment elevation myocardial infarction (STEMI). Results: there was a reduction of 14.7% in admission rate for acute myocardial infarction (AMI) during the peri-lockdown period. The 3-month mortality rate did not differ significantly (6.9% in 2020 vs. 10.5% in 2019, p = 0.341 for STEMI patients; 5.3% in 2020 vs. 2.6% in 2019, p = 0.374 for patients with acute myocardial infarction without ST segment elevation (NSTEMI)). More STEMI patients presented with Killip IV class in 2019 (13.5% vs. 5.5%, p = 0.043, respectively). There was an increase of door-to-PCI time (54.0 [42.0-86.0] in 2019; 63.5 [48.3-97.5] in 2020, p = 0.018) and first medical contact (FMC)-to-PCI time (101.0 [82.5-120.8] in 2019; 115 [97.0-154.5] in 2020, p = 0.01) during the pandemic period. Conclusions: There was a 14.7% reduction of admissions for AMI during the first wave of COVID-19. FMC-to-PCI time increased during the peri-lockdown period, however, it did not translate into worse survival during follow-up.

Self-Care Monitoring of Heart Failure Symptoms and Lung Impedance at Home Following Hospital Discharge: Longitudinal Study.

BACKGROUND: Self-care is key to the daily management of chronic heart failure (HF). After discharge from hospital, patients may struggle to recognize and respond to worsening HF symptoms. Failure to monitor and respond to HF symptoms may lead to unnecessary hospitalizations. OBJECTIVE: This study aimed to (1) determine the feasibility of lung impedance measurements and a symptom diary to monitor HF symptoms daily at home for 30 days following hospital discharge and (2) determine daily changes in HF symptoms of pulmonary edema, lung impedance measurements, and if self-care behavior improves over time when patients use these self-care monitoring tools. METHODS: This study used a prospective longitudinal design including patients from cardiology wards in 2 university hospitals-one in Norway and one in Lithuania. Data on HF symptoms and pulmonary edema were collected from 10 participants (mean age 64.5 years; 90% (9/10) male) with severe HF (New York Heart Association classes III and IV) who were discharged home after being hospitalized for an HF condition. HF symptoms were self-reported using the Memorial Symptom Assessment Scale for Heart Failure. Pulmonary edema was measured by participants using a noninvasive lung impedance monitor, the CardioSet Edema Guard Monitor. Informal caregivers aided the participants with the noninvasive measurements. RESULTS: The prevalence and burden of shortness of breath varied from participants experiencing them daily to never, whereas lung impedance measurements varied for individual participants and the group participants, as a whole. Self-care behavior score improved significantly (P=.007) from a median of 56 (IQR range 22-75) at discharge to a median of 81 (IQR range 72-98) 30 days later. CONCLUSIONS: Noninvasive measurement of lung impedance daily and the use of a symptom diary were feasible at home for 30 days in HF patients. Self-care behavior significantly improved after 30 days of using a symptom diary and measuring lung impedance at home. Further research is needed to determine if daily self-care monitoring of HF signs and symptoms, combined with daily lung impedance measurements, may reduce hospital readmissions.

The effect of cardiac shock wave therapy on myocardial function and perfusion in the randomized, triple-blind, sham-procedure controlled study.

BACKGROUND: Recent triple-blind sham procedure-controlled study revealed neutral effects of the cardiac shock wave therapy (CSWT) on exercise tolerance and symptoms in patients with stable angina. Current data about the effects of CSWT on global and regional myocardial contractility and perfusion is limited. Hereby we report the results of an imaging sub-study that evaluated the capacity of CSWT to ameliorate myocardial ischemia induced during dobutamine stress echocardiography (DSE) and cardiac single photon emission computed tomography (SPECT). METHODS: Prospective, randomized, triple-blind, sham procedure-controlled study enrolled 72 adult subjects who complied with defined inclusion criteria. The subjects were assigned to the OMT + CSWT and the OMT + sham procedure study groups with 1:1 ratio. Application of the CSWT covered all segments of the left ventricle. Imaging ischemia tests were performed in 59 study patients: DSE and SPECT before the CSWT treatment and after 6 months, with DSE carried out additionally at 3 months after randomization. Co-primary endpoints of the study were: change in wall motion score index (WMSI), representing the stress-induced impairment of regional myocardial function, and change in summed difference score (SDS), representing the amount of perfusion defect. RESULTS: OMT + CSWT and OMT + sham procedure study groups included 30 and 29 patients, respectively. Regional myocardial contractility during DSE significantly improved at 3 months follow-up in OMT + CSWT group compared to baseline as shown by WMSI at stress (1.4 ± 0.4 vs 1.6 ± 0.4, p = 0.001), but not in OMT + sham procedure group (1.5 ± 0.3 vs 1.6 ± 0.4, p = 0.136). The difference in stress DSE results between both study groups disappeared after 6 months. SPECT results demonstrated a significant reduction of inducible ischemia in OMT + CSWT group compared to OMT + sham procedure group at 6 months follow-up (SDS dropped from 5.4 ± 3.7 to 3.6 ± 3.8 vs 6.4 ± 5.9 to 6.2 ± 5 respectively, p = 0.034). CONCLUSIONS: Cardiac shock wave treatment showed the ability to reduce stress-induced myocardial ischemia, as assessed by wall motion abnormalities and perfusion defects, compared to sham procedure. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02339454 ). The trial was registered retrospectively on 12 January 2015.

Left ventricular function monitoring in heart failure.

Imaging modalities are used for screening, risk stratification and monitoring of heart failure (HF). In particular, echocardiography represents the cornerstone in the assessment of left ventricular (LV) dysfunction. Despite the well-known limitations of LV ejection fraction, this parameter, repeated assessment of LV function is recommended for the diagnosis and care of patients with HF and provides prognostic information. Left ventricular ejection fraction (LVEF) has an essential role in phenotyping and appropriate guiding of the therapy of patients with chronic HF. This document reflects the key points concerning monitoring LV function discussed at a consensus meeting on physiological monitoring in the complex multi-morbid HF patient under the auspices of the Heart Failure Association of the ESC.

Health Care Professionals' Perceptions of Home Telemonitoring in Heart Failure Care: Cross-Sectional Survey.

BACKGROUND: Noninvasive telemonitoring (TM) can be used in heart failure (HF) patients to perform early detection of decompensation at home, prevent unnecessary health care utilization, and decrease health care costs. However, the evidence is not sufficient to be part of HF guidelines for follow-up care, and we have no knowledge of how TM is used in the Nordic Baltic region. OBJECTIVE: The aim of this study was to describe health care professionals' (HCPs) perception of and presumed experience with noninvasive TM in daily HF patient care, perspectives of the relevance of and reasons for applying noninvasive TM, and barriers to the use of noninvasive TM. METHODS: A cross-sectional survey was performed between September and December 2016 in Norway and Lithuania with physicians and nurses treating HF patients at either a hospital ward or an outpatient clinic. A total of 784 questionnaires were sent nationwide by postal mail to 107 hospitals. The questionnaire consisted of 43 items with close- and open-ended questions. In Norway, the response rate was 68.7% (226/329), with 57 of 60 hospitals participating, whereas the response rate was 68.1% (310/455) in Lithuania, with 41 of 47 hospitals participating. Responses to the closed questions were analyzed using descriptive statistics, and the open-ended questions were analyzed using summative content analysis. RESULTS: This study showed that noninvasive TM is not part of the current daily clinical practice in Norway or Lithuania. A minority of HCPs responded to be familiar with noninvasive TM in HF care in Norway (48/226, 21.2%) and Lithuania (64/310, 20.6%). Approximately half of the HCPs in both countries perceived noninvasive TM to be relevant in follow-up of HF patients in Norway (131/226, 58.0%) and Lithuania (172/310, 55.5%). For physicians in both countries and nurses in Norway, the 3 most mentioned reasons for introducing noninvasive TM were to improve self-care, to reduce hospitalizations, and to provide high-quality care, whereas the Lithuanian nurses described ability to treat more patients and to reduce their workload as reasons for introducing noninvasive TM. The main barriers to implement noninvasive TM were lack of funding from health care authorities or the Territorial Patient Fund. Moreover, HCPs perceive that HF patients themselves could represent barriers because of their physical or mental condition in addition to a lack of internet access. CONCLUSIONS: HCPs in Norway and Lithuania are currently nonusers of TM in daily HF care. However, they perceive a future with TM to improve the quality of care for HF patients. Financial barriers and HF patients' condition may have an impact on the use of TM, whereas sufficient funding from health care authorities and improved knowledge may encourage the more widespread use of TM in the Nordic Baltic region and beyond.