Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year. Objective: To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up. Design, Setting, and Participants: The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle. Interventions: Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy. Main outcomes and measures: The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions. Results: Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, -188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (-28 [95% CI, -63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points. Conclusions and Relevance: In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior. Trial registration: ClinicalTrials.gov Identifier: NCT03208153.

Three-dimensional aortic geometry mapping via registration of non-gated contrast-enhanced or gated and respiratory-navigated MR angiographies.

BACKGROUND: The measurement of aortic dimensions and their evolution are key in the management of patients with aortic diseases. Manual assessment, the current guideline-recommended method and clinical standard, is subjective, poorly reproducible, and time-consuming, limiting the capacity to track aortic growth in everyday practice. Aortic geometry mapping (AGM) via image registration of serial computed tomography angiograms outperforms manual assessment, providing accurate and reproducible 3D maps of aortic diameter and growth rate. This observational study aimed to evaluate the accuracy and reproducibility of AGM on non-gated contrast-enhanced (CE-) and cardiac- and respiratory-gated (GN-) magnetic resonance angiographies (MRA). METHODS: Patients with thoracic aortic disease followed with serial CE-MRA (n = 30) or GN-MRA (n = 15) acquired at least 1 year apart were retrospectively and consecutively identified. Two independent observers measured aortic diameters and growth rates (GR) manually at several thoracic aorta reference levels and with AGM. Agreement between manual and AGM measurements and their inter-observer reproducibility were compared. Reproducibility for aortic diameter and GR maps assessed with AGM was obtained. RESULTS: Mean follow-up was 3.8 ± 2.3 years for CE- and 2.7 ± 1.6 years for GN-MRA. AGM was feasible in the 93% of CE-MRA pairs and in the 100% of GN-MRA pairs. Manual and AGM diameters showed excellent agreement and inter-observer reproducibility (ICC>0.9) at all anatomical levels. Agreement between manual and AGM GR was more limited, both in the aortic root by GN-MRA (ICC=0.47) and in the thoracic aorta, where higher accuracy was obtained with GN- than with CE-MRA (ICC=0.55 vs 0.43). The inter-observer reproducibility of GR by AGM was superior compared to manual assessment, both with CE- (thoracic: ICC= 0.91 vs 0.51) and GN-MRA (root: ICC=0.84 vs 0.52; thoracic: ICC=0.93 vs 0.60). AGM-based 3D aortic size and growth maps were highly reproducible (median ICC >0.9 for diameters and >0.80 for GR). CONCLUSION: Mapping aortic diameter and growth on MRA via 3D image registration is feasible, accurate and outperforms the current manual clinical standard. This technique could broaden the possibilities of clinical and research evaluation of patients with aortic thoracic diseases.

Impact of a successful percutaneous mitral paravalvular leak closure on long-term major clinical outcomes.

BACKGROUND: Percutaneous mitral paravalvular leak (PVL) closure techniques are an effective and safe alternative to surgical treatment, but data regarding long-term outcomes are scarce. We aim to describe the impact of successful percutaneous mitral PVL closure on long-term outcomes. METHODS: All consecutive patients in whom a first-attempt percutaneous mitral PVL closure was performed in a single tertiary center between January 2010 and October 2021 were included. Clinical variables, procedural details and procedural success were collected. Patients were classified based on procedural success, defined as no more than mild residual leak. All-cause mortality was the primary endpoint. Cardiovascular death and heart failure hospitalizations (HFH) were key secondary endpoints. RESULTS: Ninety patients (median age 72.5 years [66.0-78.4]; median Euroscore-II 8.2 [5.3-12.46]) were included. Although reduction of at least one degree in PVL severity was achieved in 82 (91.1%), procedural success was achieved in 47 (52.2%). Chronic kidney disease, previous surgery for PVL, and the presence of multiple jets, were independently associated with procedural failure. After a median follow-up of 3.2 (1.2-5.2) years, mortality rate was higher in the procedural failure group (27.3 per 100 patients-years) compared to the group with successful closure (8.2 per 100 patient-years). Procedural failure was associated with all-cause death (adjusted hazard ratio [aHR]:2.59; 95%CI:1.41-4.78), cardiovascular death (aHR:3.53, 95%CI:1.67-7.49) and HFH (aHR:3.27, 95%CI:1.72-6.20). CONCLUSIONS: A successful reduction in PVL to mild or absent is associated with improved rates of all-cause death, cardiovascular death and HFH.

Fulminant myocarditis following SARS-CoV-2 mRNA vaccination rescued with venoarterial ECMO: A report of two cases.

INTRODUCTION: Cases of myocarditis after COVID-19 messenger RNA (mRNA) vaccines administration have been reported. Although the majority follow a mild course, fulminant presentations may occur. In these cases, cardiopulmonary support with venoarterial extracorporeal membrane oxygenation (V-A ECMO) may be needed. RESULTS: We present two cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-CoV2 vaccine. One of the cases was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab using the Seldinger technique. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Whereas an endomyocardial biopsy was performed in both, a definite microscopic diagnosis just could be reached in one of them. Treatment was the same, using 1000mg of methylprednisolone/day for three days. A cardiac magnetic resonance was performed ten days after admission, showing a significant improvement of the left ventricular ejection fraction and diffuse oedema and subepicardial contrast intake in different segments. Both cases were discharged fully recovered, with CPC 1. CONCLUSIONS: COVID-19 vaccine-associated fulminant myocarditis has a high morbidity and mortality but presents a high potential for recovery. V-A ECMO should be established in cases with refractory cardiogenic shock during the acute phase.

Spontaneous reperfusion enhances succinate concentration in peripheral blood from stemi patients but its levels does not correlate with myocardial infarct size or area at risk.

Succinate is enhanced during initial reperfusion in blood from the coronary sinus in ST-segment elevation myocardial infarction (STEMI) patients and in pigs submitted to transient coronary occlusion. Succinate levels might have a prognostic value, as they may correlate with edema volume or myocardial infarct size. However, blood from the coronary sinus is not routinely obtained in the CathLab. As succinate might be also increased in peripheral blood, we aimed to investigate whether peripheral plasma concentrations of succinate and other metabolites obtained during coronary revascularization correlate with edema volume or infarct size in STEMI patients. Plasma samples were obtained from peripheral blood within the first 10 min of revascularization in 102 STEMI patients included in the COMBAT-MI trial (initial TIMI 1) and from 9 additional patients with restituted coronary blood flow (TIMI 2). Metabolite concentrations were analyzed by 1H-NMR. Succinate concentration averaged 0.069 ± 0.0073 mmol/L in patients with TIMI flow ≤ 1 and was significantly increased in those with TIMI 2 at admission (0.141 ± 0.058 mmol/L, p < 0.05). However, regression analysis did not detect any significant correlation between most metabolite concentrations and infarct size, extent of edema or other cardiac magnetic resonance (CMR) variables. In conclusion, spontaneous reperfusion in TIMI 2 patients associates with enhanced succinate levels in peripheral blood, suggesting that succinate release increases overtime following reperfusion. However, early plasma levels of succinate and other metabolites obtained from peripheral blood does not correlate with the degree of irreversible injury or area at risk in STEMI patients, and cannot be considered as predictors of CMR variables.Trial registration: Registered at www.clinicaltrials.gov (NCT02404376) on 31/03/2015. EudraCT number: 2015-001000-58.

Código shock cardiogénico 2023. Documento de expertos para una organización multidisciplinaria que permita una atención de calidad / Cardiogenic shock code 2023. Expert document for a multidisciplinary organization that allows quality care

Pese a los esfuerzos realizados para mejorar la atención al shock cardiogénico (SC), incluyendo el desarrollo de dispositivos de asistencia circulatoria mecánica (ACM), su pronóstico continúa siendo desfavorable. En este contexto surgen iniciativas de código SC, basadas en proporcionar una asistencia rápida y de calidad a estos pacientes. Este documento multidisciplinario trata de justificar la necesidad de implantar el código SC, definiendo su estructura/organización, criterios de activación, flujo de pacientes según nivel asistencial e indicadores de calidad. Sus propósitos concretos son: a) presentar las peculiaridades de esta enfermedad y el aprendizaje del código infarto y de experiencias previas en SC; b) detallar las bases para el abordaje de estos pacientes, la estructura de los equipos, su logística, la elección del tipo de ACM y el momento de su implante, y c) abordar los desafíos para la implantación del código SC, como la singularidad del código SC pediátrico. Urge desarrollar una asistencia protocolizada, multidisciplinaria y centralizada en hospitales con gran volumen y experiencia que permita minimizar la inequidad en el acceso a la ACM y mejorar la supervivencia de estos enfermos. Solo el apoyo institucional y estructural de las distintas administraciones permitirá optimizar la atención al SC (AU)

Despite the efforts made to improve the care of cardiogenic shock (CS) patients, including the development of mechanical circulatory support (MCS), the prognosis of these patients continues to be poor. In this context, CS code initiatives arise, based on providing adequate, rapid, and quality care to these patients. In this multidisciplinary document we try to justify the need to implement the SC code, defining its structure/organization, activation criteria, patient flow according to care level, and quality indicators. Our specific purposes are: a) to present the peculiarities of this condition and the lessons of infarction code and previous experiences in CS; b) to detail the structure of the teams, their logistics and the bases for the management of these patients, the choice of the type of MCS, and the moment of its implantation, and c) to address challenges to SC code implementation, including the uniqueness of the pediatric SC code. There is an urgent need to develop protocolized, multidisciplinary, and centralized care in hospitals with a large volume and experience that will minimize inequity in access to the MCS and improve the survival of these patients. Only institutional and structural support from the different administrations will allow optimizing care for CS (AU)

Effect of Routine Invasive vs Conservative Strategy in Older Adults With Frailty and Non-ST-Segment Elevation Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance: To our knowledge, no randomized clinical trial has compared the invasive and conservative strategies in frail, older patients with non-ST-segment elevation acute myocardial infarction (NSTEMI). Objective: To compare outcomes of invasive and conservative strategies in frail, older patients with NSTEMI at 1 year. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted at 13 Spanish hospitals between July 7, 2017, and January 9, 2021, and included 167 older adult (≥70 years) patients with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. Data analysis was performed from April 2022 to June 2022. Interventions: Patients were randomized to routine invasive (coronary angiography and revascularization if feasible; n = 84) or conservative (medical treatment with coronary angiography for recurrent ischemia; n = 83) strategy. Main Outcomes and Measures: The primary end point was the number of days alive and out of the hospital (DAOH) from discharge to 1 year. The coprimary end point was the composite of cardiac death, reinfarction, or postdischarge revascularization. Results: The study was prematurely stopped due to the COVID-19 pandemic when 95% of the calculated sample size had been enrolled. Among the 167 patients included, the mean (SD) age was 86 (5) years, and mean (SD) Clinical Frailty Scale score was 5 (1). While not statistically different, DAOH were about 1 month (28 days; 95% CI, -7 to 62) greater for patients managed conservatively (312 days; 95% CI, 289 to 335) vs patients managed invasively (284 days; 95% CI, 255 to 311; P = .12). A sensitivity analysis stratified by sex did not show differences. In addition, we found no differences in all-cause mortality (hazard ratio, 1.45; 95% CI, 0.74-2.85; P = .28). There was a 28-day shorter survival in the invasive vs conservatively managed group (95% CI, -63 to 7 days; restricted mean survival time analysis). Noncardiac reasons accounted for 56% of the readmissions. There were no differences in the number of readmissions or days spent in the hospital after discharge between groups. Neither were there differences in the coprimary end point of ischemic cardiac events (subdistribution hazard ratio, 0.92; 95% CI, 0.54-1.57; P = .78). Conclusions and Relevance: In this randomized clinical trial of NSTEMI in frail older patients, there was no benefit to a routine invasive strategy in DAOH during the first year. Based on these findings, a policy of medical management and watchful observation is recommended for older patients with frailty and NSTEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03208153.

Cardiogenic shock code 2023. Expert document for a multidisciplinary organization that allows quality care.

Despite the efforts made to improve the care of cardiogenic shock (CS) patients, including the development of mechanical circulatory support (MCS), the prognosis of these patients continues to be poor. In this context, CS code initiatives arise, based on providing adequate, rapid, and quality care to these patients. In this multidisciplinary document we try to justify the need to implement the SC code, defining its structure/organization, activation criteria, patient flow according to care level, and quality indicators. Our specific purposes are: a) to present the peculiarities of this condition and the lessons of infarction code and previous experiences in CS; b) to detail the structure of the teams, their logistics and the bases for the management of these patients, the choice of the type of MCS, and the moment of its implantation, and c) to address challenges to SC code implementation, including the uniqueness of the pediatric SC code. There is an urgent need to develop protocolized, multidisciplinary, and centralized care in hospitals with a large volume and experience that will minimize inequity in access to the MCS and improve the survival of these patients. Only institutional and structural support from the different administrations will allow optimizing care for CS.

Acute LDL-C reduction post ACS: strike early and strike strong: from evidence to clinical practice. A clinical consensus statement of the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Association of Preventive Cardiology (EAPC) and the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

After experiencing an acute coronary syndrome (ACS), patients are at a high risk of suffering from recurrent ischaemic cardiovascular events, especially in the very early phase. Low density lipoprotein-cholesterol (LDL-C) is causally involved in atherosclerosis and a clear, monotonic relationship between pharmacologic LDL-C lowering and a reduction in cardiovascular events post-ACS has been shown, a concept termed 'the lower, the better'. Current ESC guidelines suggest an LDL-C guided, step-wise initiation and escalation of lipid-lowering therapy (LLT). Observational studies consistently show low rates of guideline-recommended LLT adaptions and concomitant low rates of LDL-C target goal achievement, leaving patients at residual risk, especially in the vulnerable post-ACS phase. In addition to the well-established 'the lower, the better' approach, a 'strike early and strike strong' approach in the early post-ACS phase with upfront initiation of a combined lipid-lowering approach using high-intensity statins and ezetimibe seems reasonable. We discuss the rationale, clinical trial evidence and experience for such an approach and highlight existing knowledge gaps. In addition, the concept of acute initiation of PCSK9 inhibition in the early phase is reviewed. Ultimately, we focus on hurdles and solutions to provide high-quality, evidence-based follow-up care in post-ACS patients.

Impact of revascularization guided by functional testing in ischaemic cardiomyopathy.

AIMS: The burden of ischaemia is a risk factor for adverse outcomes in ischaemic cardiomyopathy (ICM) but is not systematically tested when deciding on revascularization. Limited data exists in patients with ICM regarding the interaction between ischaemia and early coronary revascularization (ECR). This study sought to determine if the burden of ischaemia modifies the outcomes of ECR in ICM. METHODS AND RESULTS: Consecutive patients with ICM (left ventricular ejection fraction < 40%) with a stress-rest gated single-photon emission computed tomography (N = 747) were followed-up for ECR and major cardiovascular events (MACEs, cardiovascular death, myocardial infarction, or heart failure hospitalization). A 1:1 matched population was selected using a propensity score for ECR. The interaction between ischaemia and ECR was evaluated in the matched cohort. In the initial cohort, 131 patients underwent ECR. Of them, 109 were matched to non-ECR patients. After a median follow up of 4.1 years, 102 (46.8%) patients experienced a MACE. The effect of revascularization on MACE was dependent of the percent of ischaemia (P for the interaction at 10% ischaemia = 0.021), so that a trend towards a decreased risk of MACE was seen in patients with >10% of ischaemia [hazard ratio (HR) = 0.59 (0.30-1.18)], whereas a non-significant increase of MACE was observed in those with <10% ischaemia (HR = 1.67 [0.94-2.96]). CONCLUSIONS: In a contemporary cohort of patients with ICM, the beneficial effects of ECR may be mediated by the percent of ischaemia. This study supports stress testing in ICM and an ischaemia-guided approach for ECR.

Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.

Despite advances in its treatment, heart failure remains a major cause of morbidity and mortality, evidencing an urgent need for novel mechanism-based targets and strategies. Myocardial hypertrophy, caused by a wide variety of chronic stress stimuli, represents an independent risk factor for the development of heart failure, and its prevention constitutes a clinical objective. Recent studies performed in preclinical animal models support the contribution of the Ca2+-dependent cysteine proteases calpains in regulating the hypertrophic process and highlight the feasibility of their long-term inhibition as a pharmacological strategy. In this review, we discuss the existing evidence implicating calpains in the development of cardiac hypertrophy, as well as the latest advances in unraveling the underlying mechanisms. Finally, we provide an updated overview of calpain inhibitors that have been explored in preclinical models of cardiac hypertrophy and the progress made in developing new compounds that may serve for testing the efficacy of calpain inhibition in the treatment of pathological cardiac hypertrophy.

Association of renin-angiotensin system blockers with COVID-19 diagnosis and prognosis in patients with hypertension: a population-based study.

BACKGROUND: The effect of renin-angiotensin system (RAS) blockade either by angiotensin-converting enzyme inhibitors (ACEis) or angiotensin-receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) susceptibility, mortality and severity is inadequately described. We examined the association between RAS blockade and COVID-19 diagnosis and prognosis in a large population-based cohort of patients with hypertension (HTN). METHODS: This is a cohort study using regional health records. We identified all individuals aged 18-95 years from 87 healthcare reference areas of the main health provider in Catalonia (Spain), with a history of HTN from primary care records. Data were linked to COVID-19 test results, hospital, pharmacy and mortality records from 1 March 2020 to 14 August 2020. We defined exposure to RAS blockers as the dispensation of ACEi/ARBs during the 3 months before COVID-19 diagnosis or 1 March 2020. Primary outcomes were: COVID-19 infection and severe progression in hospitalized patients with COVID-19 (the composite of need for invasive respiratory support or death). For both outcomes and for each exposure of interest (RAS blockade, ACEi or ARB) we estimated associations in age-, sex-, healthcare area- and propensity score-matched samples. RESULTS: From a cohort of 1 365 215 inhabitants we identified 305 972 patients with HTN history. Recent use of ACEi/ARBs in patients with HTN was associated with a lower 6-month cumulative incidence of COVID-19 diagnosis {3.78% [95% confidence interval (CI) 3.69-3.86%] versus 4.53% (95% CI 4.40-4.65%); P < 0.001}. In the 12 344 patients with COVID-19 infection, the use of ACEi/ARBs was not associated with a higher risk of hospitalization with need for invasive respiratory support or death [OR = 0.91 (0.71-1.15); P = 0.426]. CONCLUSIONS: RAS blockade in patients with HTN is not associated with higher risk of COVID-19 infection or with a worse progression of the disease.