Is premorbid stress assessed by hair cortisol concentration linked to Takotsubo syndrome? Results from a pilot study.

INTRODUCTION: The pathophysiology of Takotsubo syndrome (TTS) is not completely understood and the role of chronic stress is among the main mechanistic links. The aim of this study was to explore whether accumulating hair cortisol concentration (HCC), a novel biomarker of chronic stress, is associated with the occurrence of TTS. METHODS: A consecutive series of 18 TTS patients and 36 age and sex matched healthy controls were included in our analysis. Hair samples were collected from participants' vertex. The proximal 2.5 cm of hair was cut in equal parts of 0.5 cm, reflecting mean cortisol levels in time intervals of 0-15, 15-30, 30-45, 45-60 and 60-75 days prior to hair collection. RESULTS: HCC was higher in TTS group compared to controls at any time point and increased over time starting from 75 days prior to the event. The rate of HCC increase was significantly higher in TTS patients versus controls (beta of interaction = 0.48; 95%CI: 0.36-0.60; p < 0.001). CONCLUSIONS: The steadily increasing trend of HCC in TTS patients suggests that the additive effect of multiple stressful events over several weeks prior TTS onset may disrupt cortisol homeostasis and play a role in TTS pathophysiology.

NT-proBNP/cardiac troponin T ratio >7.5 on the second day of admission can differentiate Takotsubo from acute coronary syndrome with good accuracy.

BACKGROUND: Takotsubo syndrome (TTS) is not usually diagnosed until patients with suspected acute coronary syndrome (ACS) and echocardiographically detected apical aneurysm are found to have "normal" coronary angiography (CA). Our aim was to explore whether cardiac biomarkers can contribute to the early diagnosis of TTS. METHODS: Ratios of N-terminal-pro brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT) both expressed in pg/mL [admission and the 3 following days] were compared in 38 patients with TTS and 114 ACS patients of whom 58 had non-ST-elevation myocardial infarction (NSTEMI). RESULTS: NT-proBNP/cTnT ratio at admission and during the following 3 days was significantly higher in TTS compared to patients with ACS [18.4 (8.7-41.7) vs 2.9 (0.8-6.8), 29.6 (14.3-53.7) vs 1.2 (0.5-2.7), 30.0 (11.6-50.9) vs 1.7 (0.5-3.0), 27.8 (11.3-42.6) vs 1.4 (0.6-2.8), respectively, all <0.001]. Βest discrimination of TTS from ACS was possible with the ratio of NT-proBNP/cTnT on the 2nd day. A cut-off value of NT-proBNP/cTnT ratio >7.5 had a sensitivity of 97.3%, a specificity of 95.4% and an accuracy of ∼96% in detecting TTS as opposed to ACS. Furthermore, the ratio of NT-proBNP/cTnT preserved its discriminatory value in the subgroup of patients with NSTEMI. In particular, an NT-proBNP/cTnT ratio >7.5 on the 2nd day had a sensitivity of 97.3%, a specificity of 91.4%, and an accuracy of 93.7% in differentiating TTS from NSTEMI. CONCLUSIONS: An NT-proBNP/cTnT ratio >7.5 on the 2nd day of admission can be useful for the early identification of TTS among selected patients initially presenting with ACS, a ratio more clinically useful in the setting of NSTEMI.

Infection as an under-recognized precipitant of acute heart failure: prognostic and therapeutic implications.

As the prevalence of heart failure (HF) continues to rise, prompt diagnosis and management of various medical conditions, which may lead to HF exacerbation and result in poor patient outcomes, are of paramount importance. Infection has been identified as a common, though under-recognized, precipitating factor of acute heart failure (AHF), which can cause rapid development or deterioration of HF signs and symptoms. Available evidence indicates that infection-related hospitalizations of patients with AHF are associated with higher mortality, protracted length of stay, and increased readmission rates. Understanding the intricate interaction of both clinical entities may provide further therapeutic strategies to prevent the occurrence of cardiac complications and improve prognosis of patients with AHF triggered by infection. The purpose of this review is to investigate the incidence of infection as a causative factor in AHF, explore its prognostic implications, elucidate the underlying pathophysiological mechanisms, and highlight the basic principles of the initial diagnostic and therapeutic interventions in the emergency department.

Impaired Endothelial Glycocalyx Predicts Adverse Outcome in Subjects Without Overt Cardiovascular Disease: a 6-Year Follow-up Study.

We investigated whether disturbance of glycocalyx integrity is related with increased cardiovascular risk. In 600 healthy subjects, we measured perfused boundary region (PBR), a marker of glycocalyx integrity, in sublingual microvessels with diameter ranging 5-25 µm using a dedicated camera (Sideview Darkfield Imaging). Increased PBR indicates reduced glycocalyx thickness. We prospectively monitored the occurrence of cardiovascular events (MACE-death, myocardial infarction, and stroke) during a 6-year follow-up. Fifty-seven MACE were documented. Increased values of PBR5-25 predicted higher risk for MACE in a model including sex, age, hyperlipidemia, diabetes, hypertension, smoking, family history of coronary disease, treatment with ACEi/ARBs, or lipid-lowering agents (hazard ratio (HR), 6.44, p = 0.011; net reclassification improvement (NRI), 28%; C-statistic: 0.761). PBR5-25 was an independent and additive predictor of outcome when added in a model including the European Heart SCORE, diabetes, family history of CAD, and medication (HR, 4.71; NRI: 39.7%, C-statistic from 0.653 to 0.693; p < 0.01).Glycocalyx integrity is an independent and additive predictor to risk factors for MACE at 6-year follow-up in individuals without cardiovascular disease. ClinicalTrials.govIdentifier:NCT04646252. PBR5-25 was an independent and additive predictor of adverse cardiovascular events in a model including the European Heart SCORE, diabetes, family history of coronary disease, and medication (HR: 4.71, NRI: 39.7%, C-statistic from 0.653 to 0.693; p < 0.01, NRI:37.9%).

Association between up-titration of medical therapy and total hospitalizations and mortality in patients with recent worsening heart failure across the ejection fraction spectrum.

BACKGROUND: The role of neurohormonal inhibition in chronic heart failure (HF) is well established. There are limited data on the effect of up-titration of renin-angiotensin inhibitors (RASi) and beta-blockers (BBs) on clinical outcomes of patients with worsening HF across the left ventricular ejection fraction (LVEF) spectrum. METHODS AND RESULTS: We analysed data from 2345 patients from BIOSTAT-CHF (80.9% LVEF <40%), who completed a 3-month up-titration period after recent worsening of HF. Patients were classified by achieved dose (% of recommended): ≥100%, 50-99%, 1-49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BB dose and all-cause and HF hospitalizations. In the 21 months following up-titration, 512 patients died and 879 (37.5%) had ≥1 hospitalization. RASi up-titration was associated, incrementally, with reduced risk of all-cause hospitalization at all achieved dose levels compared to no treatment [hazard ratio (95% confidence interval): ≥100%: 0.60 (0.49-0.74), P < 0.001; 50-99%: 0.56 (0.46-0.68), P < 0.001; 1-49%: 0.71 (0.59-0.86), P < 0.001]. This association was consistent up to an LVEF of 49% (P < 0.001), and when considering only HF hospitalizations. Up-titration of BBs was associated with fewer all-cause hospitalizations only when LVEF was <40% (overall P < 0.001), but with more HF hospitalizations when LVEF was ≥50%. Up-titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%. CONCLUSION: After recent worsening of HF, up-titration of RASi and BBs was associated with a better prognosis in patients with LVEF ≤49%. Up-titration of BBs was associated with a greater risk of HF hospitalization when LVEF was ≥50%.

Siblings with coronavirus disease 2019 infection and opposite outcome-the hemodialysis's better outcome paradox: Two case reports.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly contagious infection caused by the severe acute respiratory syndrome coronavirus 2 virus and has a unique underlying pathogenesis. Hemodialysis (HD) patients experience high risk of contamination with COVID-19 and are considered to have higher mortality rates than the general population by most but not all clinical series. We aim to highlight the peculiarities in the immune state of HD patients, who seem to have both immune-activation and immune-depression affecting their outcome in COVID-19 infection. CASE SUMMARY: We report the opposite clinical outcomes (nearly asymptomatic course vs death) of two diabetic elderly patients infected simultaneously by COVID-19, one being on chronic HD and the other with normal renal function. They were both admitted in our hospital with COVID-19 symptoms and received the same treatment by protocol. The non-HD sibling deteriorated rapidly and was intubated and transferred to the Intensive Care Unit, where he died despite all supportive care. The HD sibling, although considered more "high-risk" for adverse outcome, followed a benign course and left the hospital alive and well. CONCLUSION: These cases may shed light on aspects of the immune responses to COVID-19 between HD and non-HD patients and stimulate further research in pathophysiology and treatment of this dreadful disease.

A comparison of early redo surgery rates in Mosaic porcine and Perimount bovine pericardial valves.

OBJECTIVES: The objective of this study was to compare rates of redo surgery for the Medtronic Mosaic 305 A Porcine Prosthesis and the Carpentier-Edwards Perimount Pericardial Aortic Bioprosthesis 2900. METHODS: This was a single-centre retrospective observational study. We included all 1018 patients who underwent aortic valve replacement with a Mosaic (n = 216) or Perimount (n = 809) bioprosthesis between October 2000 and August 2008. The total follow-up was 1508 patient-years for the Mosaic valve and 5813 for the Perimount valve. The maximal follow-up and interquartile range were 14.8 and 7.0 years for the Mosaic valve and 15.1 and 5.6 years for the Perimount valve, respectively. A propensity score-weighted version of the Cox model, Kaplan-Meier analysis and multivariate regression model was used. RESULTS: Despite no statistical difference in the number of non-structural valve deterioration cases between valves, redo surgery occurred earlier in 10 (4.6%) Mosaic than for 17 (2.1%) Perimount valves (P = 0.02) and was required for structural valve deterioration in 5 (2.3%) Mosaic valves when compared with 7 (0.9%; P = 0.04) Perimount valves. Four of 5 Mosaic failures occurred before 5 years, whereas all Perimount failures occurred after 5 years. Redo surgery for non-structural valve deterioration occurred in 3 patients with Mosaic valves (1.4%) and no patients with Perimount valves. Surgery for the remaining patients with Perimount valves was due to infection or aortic disease. CONCLUSIONS: Early redo surgery for structural valve degeneration was uncommon but occurred earlier for the Mosaic porcine than the Perimount bovine pericardial replacement aortic valve.

Association of mineralocorticoid receptor antagonist use and in-hospital outcomes in patients with acute heart failure.

Mineralocorticoid receptor antagonists (MRAs) constitute a beneficial therapy in chronic heart failure, but their use in the acute heart failure (AHF) setting remains rather unexplored. To assess the effect of MRAs administered during hospitalization on in-hospital outcomes of patients with AHF, we performed a post-hoc analysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF). Patients of the original study cohort (n = 4953) were categorized according to in-hospital MRA treatment status as MRA-treated (n = 1439) and untreated (n = 3514) subjects. Nearest-neighbor propensity score with 1:1 matching yielded a subsample of pairs of MRA-treated and MRA-untreated patients (n = 1003 in each treatment group) that were balanced in an extensive list of baseline characteristics. In-hospital mortality between MRA-treated and untreated patients were assessed by Cox regression analysis before and after adjustment for known prognostic factors and other concomitantly administered intravenous and oral HF specific therapies. In the matched cohort, in-hospital mortality was 4.2 vs 10.8% in MRA-treated vs untreated patients. Treatment with MRAs was associated with a reduction of in-hospital mortality [HR 0.372 (95% CI, 0.261-0.532), p < 0.001]. This association remained significant after adjustment for known prognostic factors and co-administered intravenous and oral HF therapies [HR: 0.618 (95% CI, 0.383-0.995), p = 0.048]. In conclusion, MRA therapy administered during hospitalization for AHF was associated with reduced in-hospital mortality. The role of MRAs in AHF deserves further examination in adequately powered randomized controlled studies.

Multidimensional contractile reserve predicts adverse outcome in patients with severe systolic heart failure: a 4-year follow-up study.

AIMS: Left ventricular contractile reserve is a prognostic indicator for adverse outcome in patients with severe chronic heart failure with reduced ejection fraction (HFrEF). We investigated the dobutamine-induced changes of LV multidimensional deformation and their predictive value for cardiac mortality of patients with severe chronic HFrEF. METHODS AND RESULTS: In this prospective study, out of 130 patients with severe HFrEF who underwent a low-dose dobutamine stress echocardiography (LDSE) study using speckle tracking imaging, 100 patients were followed up for the occurrence of cardiac death over a period of 4 years. Compared with survivors, non-survivors (n = 32) had lower radial strain (RS) and strain rate (RSR) (10.7 ± 5.9 vs. 20.1 ± 8% and 0.5 ± 0.2 vs. 0.8 ± 0.3 L/s, P < 0.001), a smaller increase of global longitudinal strain (GLS) and strain rate after LDSE (0.9 ± 1.5 vs. -3.3 ± 3.5% and -0.1 ± 0.1 vs. -0.3 ± 0.3 L/s, P < 0.001), and a lack of change in the circumferential and radial deformation. The dobutamine-induced changes of all speckle tracking indices predicted cardiac mortality, while, among resting echocardiographic parameters, only RS and RSR predicted survival, after adjusting for age, sex, cardiomyopathy aetiology, NYHA class, AF, BNP levels, resting LVED, and LV outflow tract velocity-time integral, and their respective changes produced by dobutamine (P < 0.05). The dobutamine-induced change of GLS and resting RS were the best additive predictors of mortality with a net reclassification improvement of 0.518 (P = 0.022) CONCLUSION: In severe chronic HFrEF, resting RS and the dobutamine-induced change of GLS are independent predictors of cardiac mortality.

Acute heart failure with mid-range left ventricular ejection fraction: clinical profile, in-hospital management, and short-term outcome.

BACKGROUND: Heart failure with mid-range left ventricular ejection fraction (HFmrEF) is a poorly characterized population as it has been studied either in the context of HF with reduced (HFrEF) or preserved (HFpEF) left ventricular ejection fraction (LVEF) depending on applied LVEF cutoffs. We sought to investigate the clinical profile, in-hospital management, and short-term outcome of HFmrEF patients in comparison with those with HFrEF or HFpEF in a large acute HF cohort. METHODS AND RESULTS: The Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF) included 4953 patients hospitalized for HF in nine countries in Europe, Latin America, and Australia. Baseline characteristics, clinical presentation, in-hospital therapies, and short-term mortality (all-cause in-hospital or 30-day mortality, whichever first) were compared among HFrEF (LVEF <40%), HFmrEF (LVEF 40-49%), and HFpEF (LVEF ≥50%) patients. Among 3257 patients with documented LVEF, 52% had HFrEF, 25% HFmrEF, and 23% HFpEF. Patients with HFmrEF had a distinct demographic and clinical profile with many intermediate features between HFrEF and HFpEF. In addition, they had a higher prevalence of hypertension (p < 0.001), a lower prevalence of chronic renal disease (p = 0.003), more hospitalizations for acute coronary syndrome (p < 0.001), or infection (p = 0.003), and were more frequently treated with intravenous vasodilators compared to HFrEF or HFpEF. Adjusted short-term mortality in HFmrEF was lower than HFrEF [hazard ratio (HR) = 0.635 (0.419, 0.963), p = 0.033] but similar to HFpEF [HR = 1.026 (0.605, 1.741), p = 0.923]. CONCLUSION: Hospitalized HFmrEF patients represent a demographically and clinically diverse group with many intermediate features compared to HFrEF and HFpEF and carry a lower risk of short-term mortality than HFrEF but a similar risk with HFpEF.

Ranolazine for the prevention or treatment of atrial fibrillation: a systematic review.

The use of currently available antiarrhythmic drugs for atrial fibrillation is limited by their moderate efficacy and the considerable proarrhythmic risk. Ranolazine, an antianginal agent, has been reported to possess antiarrhythmic properties, resulting in a reduction of supraventricular and ventricular arrhythmias. We performed a systematic review of the clinical studies reporting the outcome of patients treated with ranolazine for the prevention or treatment of atrial fibrillation in various clinical settings. We searched PubMed and abstracts of major conferences for clinical studies using ranolazine, either alone or in combination with other antiarrhythmic agents for the prevention or treatment of atrial fibrillation. Ten relevant records were identified. These included both randomized trials and retrospective cohort studies concerning the use of ranolazine in different clinical settings; prevention of atrial fibrillation in patients with acute coronary syndrome, prevention as well as conversion of postoperative atrial fibrillation after coronary artery bypass grafting, conversion of recent-onset atrial fibrillation, sinus rhythm maintenance in drug-resistant recurrent atrial fibrillation and facilitation of electrical cardioversion in cardioversion-resistant patients. A beneficial, mostly modest effect of ranolazine was homogeneously reported in all clinical settings. There were no substantial proarrhythmic effects. No meta-analysis could be performed because for most of the clinical scenarios, there was only one study investigating the effect of ranolazine. Except for one large randomized trial, all the other studies were either relatively small randomized studies or retrospective cohort analyses, which in several cases lacked a control group. This systematic review indicates a modest beneficial effect of ranolazine administered for the prevention or treatment of atrial fibrillation across several clinical settings without substantial proarrhythmic risk.

The Effects of Ranolazine on Paroxysmal Atrial Fibrillation in Patients with Coronary Artery Disease: A Preliminary Observational Study.

The impact of ranolazine, an anti-ishemic agent with antiarrhythmic properties, on paroxysmal atrial fibrillation (PAF) in patients with coronary artery disease (CAD) remains unclear. Pacing devices can be useful tools for disclosing even asymptomatic PAF. Purpose of this study is to assess the effect of ranolazine on atrial fibrillation (AF), in patients with CAD, PAF and a dual-chamber pacemaker. We studied 74 patients with CAD, PAF, and sick sinus syndrome or atrio-ventricular block, treated with pacemakers capable to detect PAF episodes. The total time in AF, AF burden, and the number of PAF episodes within the last 6 months before enrolment in the study, mean AF duration per episode, and the QTc interval were initially assessed. Subsequently, patients were randomized into additional treatment with ranolazine (375 mg twice daily) or placebo. Following six months of treatment, all parameters were reassessed and compared to those before treatment. Ranolazine was associated with shorter total AF duration (81.56±45.24 hours versus 68.71±34.84 hours, p=0.002), decreased AF burden (1.89±1.05% versus 1.59±0.81%, p=0.002), and shortened mean AF duration (1.15±0.41 hours versus 0.92±0.35 hours, p=0.01). In the placebo group no such differences were observed. In both groups, no significant differences in the number of PAF episodes and QTc duration were observed. We conclude that in patients with CAD and PAF, ranolazine reduces the total time in AF, AF burden, and mean AF duration. These findings may imply additional antiarrhythmic properties of ranolazine on atrial myocardium and might indicate the necessity of its use in ischemic patients with PAF.

Continuous chest compressions improve survival and neurologic outcome in a swine model of prolonged ventricular fibrillation.

INTRODUCTION: Evidence suggests that any interruptions, including those of rescue breaths, during cardiopulmonary resuscitation (CPR) have significant, detrimental effects on survival. The 2010 International Liaison Committee on Resuscitation guidelines strongly emphasized on the importance of minimizing interruptions during chest compressions. However, those guidelines also stress the need for ventilations in the case of prolonged cardiac arrest (CA), and it is not at present clear at which point of CA the necessity of providing ventilations overcomes the hemodynamic compromise caused by chest compressions' interruption. METHODS: Ventricular fibrillation was electrically induced in 20 piglets (19 ± 2 kg) and left untreated for 8 minutes. Animals were randomized to receive 2 minutes of either chest compression-only CPR (group CC) or standard 30:2 compressions/ventilations CPR (group S) before defibrillation. Resuscitated animals were monitored under anesthesia for 4 hours and then were awakened and placed in a maintenance facility for 24 hours. RESULTS: There was no significant difference among groups for both return of spontaneous circulation and 1-hour survival. There was a significant difference in 24-hour survival (group CC, 7/10 vs group S, 2/10; P = .025). Blood lactate levels were significantly lower in group CC compared with group S in both 1 (P = .019) and 4 hours (P = .034) after return of spontaneous circulation. Furthermore, group CC animals exhibited significantly higher mean Neurologic Alertness Score (58 ± 42.4 vs 8 ± 16.9) (P < .05). CONCLUSION: In this swine CA model, where defibrillation was first attempted at 10 minutes of untreated ventricular fibrillation, uninterrupted chest compressions resulted in significantly higher survival rates and higher 24-hour neurologic scores, compared with standard 30:2 CPR.