Impact of the Timing of Mechanical Circulatory Support on the Outcomes in Myocardial Infarction-Related Cardiogenic Shock: Subanalysis of the PREPARE CS Registry.

(1) Background: Mechanical circulatory support (MCS) in myocardial infarction-associated cardiogenic shock is subject to debate. This analysis aims to elucidate the impact of MCS's timing on patient outcomes, based on data from the PREPARE CS registry. (2) Methods: The PREPARE CS prospective registry includes patients who experienced cardiogenic shock (SCAI classes C-E) and were subsequently referred for cardiac catheterization. Our present analysis included a subset of this registry, in whom MCS was used and who underwent coronary intervention due to myocardial infarction. Patients were categorized into an Upfront group and a Procedural group, depending on the timing of MCS's introduction in relation to their PCI. The endpoint was in-hospital mortality. (3) Results: In total, 71 patients were included. MCS was begun prior to PCI in 33 (46%) patients (Upfront), whereas 38 (54%) received MCS during or after the initiation of PCI (Procedural). The groups' baseline characteristics and hemodynamic parameters were comparable. The Upfront group had a higher utilization of the Impella® device compared to extracorporeal membrane oxygenation (67% vs. 33%), while the Procedural group exhibited a balanced use of both (50% vs. 50%). Most patients suffered from multi-vessel disease in both groups (82% vs. 84%, respectively; p = 0.99), and most patients required a complex PCI procedure; the latter was more prevalent in the Upfront group (94% vs. 71%, respectively; p = 0.02). Their rates of complete revascularization were comparable (52% vs. 34%, respectively; p = 0.16). Procedural CPR was significantly more frequent in the Procedural group (45% vs. 79%, p < 0.05); however, in-hospital mortality was similar (61% vs. 79%, respectively; p = 0.12). (4) Conclusions: The upfront implantation of MCS in myocardial infarction-associated CS did not provide an in-hospital survival benefit.

Outcomes of ECLS-SHOCK Eligibility Criteria Applied to a Real-World Cohort.

BACKGROUND: Cardiogenic shock (CS) exhibits high (~50%) in-hospital mortality. The recently published Extracorporeal life Support in Cardiogenic Shock (ECLS-SHOCK) trial demonstrated the neutral effects of the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on all-cause death, as well as on all secondary outcomes in subjects presenting with myocardial-infarction (MI)-related CS. Here, we compared ECLS-SHOCK eligibility criteria with a real-world cohort of CS patients. METHODS AND RESULTS: ECLS-SHOCK eligibility criteria were applied to a prospective single-center CS registry (the PREPARE CS registry) consisting of 557 patients who were consecutively admitted to the catheterization laboratory (cath lab) of the Medical University of Graz, Austria, due to CS (SCAI C-E). Overall use of mechanical circulatory support (MCS) in this cohort was 19%. Sixty-nine percent of the entire cohort had MI-related CS, 38% of whom would have met ECLS-SHOCK eligibility criteria, thus representing only 27% of the PREPARE CS registry. Exclusion from the ECLS-SHOCK trial was based on patients with initial lactate values below 3 mmol/L (n = 168; 43.6%), aged over 80 years (n = 65; 16.9%), and with a duration of cardiopulmonary resuscitation (CPR) exceeding 45 min (n = 22; 5.7%). The 30-day mortality of patients of the PREPARE CS registry who met the ECLS-SHOCK eligibility criteria was 57.0%, compared to 48.4% of patients in the ECLS-SHOCK trial. The patients' baseline characteristics, however, differed considerably with respect to type of infarction, age, and gender. CONCLUSIONS: In a real-world cohort of patients with MI-related CS, only 38% of patients met the eligibility criteria of the ECLS-SHOCK trial. Thus, the impact of the use of VA-ECMO on outcome parameters in MI-related CS, as observed in the ECLS-SHOCK trial, may differ in a more heterogeneous real-world CS population of the PREPARE CS registry.

May Measurement Month 2018-2019: an analysis of blood pressure screening results from Austria.

Arterial hypertension is a global burden leading to over 10.8 million deaths per year worldwide. May Measurement Month (MMM) is a global project initiated by the International Society of Hypertension to raise the awareness of high blood pressure (BP) in the population. Following the MMM protocol 2508 participants ≥18 years had their BP measured in Austria in MMM18 and MMM19. Of those screened, 54.6% were found to be hypertensive, defined as a BP ≥140/90 mmHg and/or being on treatment for hypertension. Among those individuals with hypertension, 56.1% were on medication but only 42.0% of those treated had controlled BP (<140/90 mmHg). Lower BPs were found in those with previous myocardial infarction (MI), probably explained by a medical monitoring system of patients with MI in Austria. Those with hypertension were referred for further medical investigations and were provided lifestyle advice. Among a high number of individuals receiving antihypertensive treatment, BP is still not controlled. Further screening and monitoring of therapeutic effects is urgently required.

Left ventricular ejection fraction and cardiac biomarkers for dynamic prediction of cardiotoxicity in early breast cancer.

Background/Purpose: This study aims to quantify the utility of monitoring LVEF, hs-cTnT, and NT-proBNP for dynamic cardiotoxicity risk assessment in women with HER2+ early breast cancer undergoing neoadjuvant/adjuvant trastuzumab-based therapy. Materials and methods: We used joint models of longitudinal and time-to-event data to analyze 1,136 echocardiography reports and 326 hs-cTnT and NT-proBNP measurements from 185 women. Cardiotoxicity was defined as a 10% decline in LVEF below 50% and/or clinically overt heart failure. Results: Median pre-treatment LVEF was 64%, and 19 patients (10%) experienced cardiotoxicity (asymptomatic n = 12, during treatment n = 19). The pre-treatment LVEF strongly predicted for cardiotoxicity (subdistribution hazard ratio per 5% increase in pre-treatment LVEF = 0.68, 95%CI: 0.48-0.95, p = 0.026). In contrast, pre-treatment hs-cTnT and NT-proBNP were not consistently associated with cardiotoxicity. During treatment, the longitudinal LVEF trajectory dynamically identified women at high risk of developing cardiotoxicity (hazard ratio per 5% LVEF increase at any time of follow-up = 0.36, 95% CI: 0.2-0.65, p = 0.005). Thirty-four patients (18%) developed an LVEF decline ≥ 5% from pre-treatment to first follow-up ("early LVEF decline"). One-year cardiotoxicity risk was 6.8% in those without early LVEF decline and pre-treatment LVEF ≥ 60% (n = 117), 15.9% in those with early LVEF decline or pre-treatment LVEF < 60% (n = 65), and 66.7% in those with early LVEF decline and pre-treatment LVEF < 60% (n = 3), (Gray's test p < 0.0001). Conclusion: Cardiotoxicity risk is low in two thirds of women with HER2+ early breast cancer who have pre-treatment LVEF ≥ 60% and no early LVEF decline > 5% during trastuzumab-based therapy. The longitudinal LVEF trajectory but not hs-cTnT or NT-proBNP allows for a dynamic assessment of cardiotoxicity risk in this setting.

Cohort profile: 'Biomarkers of Personalised Medicine' (BioPersMed): a single-centre prospective observational cohort study in Graz/Austria to evaluate novel biomarkers in cardiovascular and metabolic diseases.

PURPOSE: Accumulating evidence points towards a close relationship between cardiovascular, endocrine and metabolic diseases. The BioPersMed Study (Biomarkers of Personalised Medicine) is a single-centre prospective observational cohort study with repetitive examination of participants in 2-year intervals. The aim is to evaluate the predictive impact of various traditional and novel biomarkers of cardiovascular, endocrine and metabolic pathways in asymptomatic individuals at risk for cardiovascular and/or metabolic disease. PARTICIPANTS: Between 2010 and 2016, we recruited 1022 regional individuals into the study. Subjects aged 45 years or older presenting with at least one traditional cardiovascular risk factor or manifest type 2 diabetes mellitus (T2DM) were enrolled. The mean age of the participants was 57±8 years, 55% were female, 18% had T2DM, 33% suffered from arterial hypertension, 15% were smokers, 42% had hyperlipidaemia, and only 26% were at low cardiovascular risk according to the Framingham 'Systematic COronary Risk Evaluation'. FINDINGS TO DATE: Study procedures during screening and follow-up visits included a physical examination and comprehensive cardiovascular, endocrine, metabolic, ocular and laboratory workup with biobanking of blood and urine samples. The variety of assessed biomarkers allows a full phenotyping of individuals at cardiovascular and metabolic risk. Preliminary data from the cohort and relevant biomarker analyses were already used as control population for genomic studies in local and international research cooperation. FUTURE PLANS: Participants will undergo comprehensive cardiovascular, endocrine and metabolic examinations for the next decades and clinical outcomes will be adjudicated prospectively.

Unfolding Cardiac Amyloidosis -From Pathophysiology to Cure.

Deposition of amyloidogenic proteins leading to the formation of amyloid fibrils in the myocardium causes cardiac amyloidosis. Although any form of systemic amyloidosis can affect the heart, light-chain (AL) or transthyretin amyloidosis (ATTR) account for the majority of diagnosed cardiac amyloid deposition. The extent of cardiac disease independently predicts mortality. Thus, the reversal of arrest of adverse cardiac remodeling is the target of current therapies. Here, we provide a condensed overview on the pathophysiology of AL and ATTR cardiac amyloidoses and describe treatments that are currently used or investigated in clinical or preclinical trials. We also briefly discuss acquired amyloid deposition in cardiovascular disease other than AL or ATTR.

A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family.

Aims: Characterization of the cardiac phenotype associated with the novel LMNA nonsense mutation c.544C>T, p.Q182*, which we have identified in a large five-generation family. Methods and results: A family tree was constructed. Clinical data [arrhythmia, syncope, sudden cardiac death (SCD), New York Heart Association (NYHA) class] were collected from living and deceased family members. DNA of 23 living family members was analysed for mutations in LMNA. Additionally, dilated cardiomyopathy multi-gene-panel testing and whole exome sequencing were performed in some family members to identify potential phenotype-modifiers. In this five-generation family (n = 65), 17 SCDs occurred at 49.3 ± 10.0 years. Furthermore, we identified eight additional mutation-carriers, seven symptomatic (44 ± 13 years), and one asymptomatic (44 years). First signs of disease [sinus bradycardia with atrioventricular (AV)-block I°] occurred at 36.5 ± 8.1 years. Paroxysmal atrial fibrillation (AF) (onset at 41.8 ± 5.7 years) rapidly progressed to permanent AF (46.2 ± 9.8 years). Subsequently, AV-conduction worsened, syncope, pacemaker-dependence, and non-sustained ventricular tachycardia (43.3 ± 8.2 years) followed. Ventricular arrhythmia caused SCD in patients without implantable cardioverter-defibrillator (ICD). Patients protected by ICD developed rapidly progressive heart failure (45.2 ± 10.6 years). A different phenotype was seen in a sub-family in three patients with early onset of rapidly decompensating heart failure and only minor prior arrhythmia-related symptoms. One patient received high-urgency heart transplantation (HTX) at 32 years, while two died prior to HTX. One of them developed lethal peripartum-associated heart failure. Possible disease-modifiers were identified in this 'heart failure sub-family'. Conclusion: The novel LMNA nonsense mutation c.544C>T causes a severe arrhythmogenic phenotype manifesting with high incidence of SCD in most patients; and in one sub-family, a distinct phenotype with fast progressing heart failure, indicating the need for early consideration of ICD-implantation and listing for heart-transplantation.