Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size. DESIGN: Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.gov NCT01529554) is a phase II randomized, double-blind, multi-center, placebo-controlled trial on the effects of a 5-day course of oral everolimus on infarct size, LV remodeling, and inflammation in patients with acute ST-elevation myocardial infarction (STEMI). Within 5 days of successful primary percutaneous coronary intervention (pPCI), patients are randomly assigned to everolimus (first 3 days: 7.5 mg every day; days 4 and 5: 5.0 mg every day) or placebo, respectively. The primary efficacy outcome is the change from baseline (defined as 12 hours to 5 days after pPCI) to 30-day follow-up in myocardial infarct size as measured by cardiac magnetic resonance imaging (CMRI). Secondary endpoints comprise corresponding changes in cardiac and inflammatory biomarkers as well as microvascular obstruction and LV volumes assessed by CMRI. Clinical events, laboratory parameters, and blood cell counts are reported as safety endpoints at 30 days. CONCLUSION: The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI.

Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

Importance: Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). Objective: To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. Design, Setting, and Participants: Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. Interventions: Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. Results: Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). Conclusions and Relevance: Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. Trial Registration: ClinicalTrials.gov Identifier: NCT00512759.

Multimodality imaging of eosinophilic myocarditis (loeffler's endocarditis) in a patient with idiopathic hypereosinophilic syndrome.

Eosinophilic myocarditis can result in endomyocardial fibrosis affecting both ventricles, leading to restrictive cardiomyopathy. Multimodality imaging is crucial for diagnosis, as demonstrated in this case of a patient presenting with symptoms of heart failure.

Postoperative Myocardial Infarction Due to Coronary Embolization of Valve Tissue After Surgical Mitral Valve Replacement.

We present the case of a 61-year-old man with known Morbus Barlow disease, who presented with postoperative myocardial infarction and cardiac arrest within 1 hour after minimally invasive mitral valve surgery owing to coronary artery occlusion by native mitral valve tissue.

Propensity Matched Outcomes of Minimally Invasive Mitral Surgery: Does a Heart-Team Approach Eliminate Female Gender as an Independent Risk Factor?

BACKGROUND: There is increasing evidence that female gender is an independent risk factor for cardiac surgery. Minimally invasive mitral surgery (MIV) has proven to have excellent long-term results, but little is known about gender-dependent outcomes. The aim of our study was to analyze our heart team's decision-based MIV-specialized cohort. METHODS: In-hospital and follow-up data were retrospectively collected. The cohort was divided into gender groups and propensity-matched groups. RESULTS: Between 22 July 2013 and 31 December 2022, 302 consecutive patients underwent MIV. Before matching, the total cohort showed that women were older, had a higher EuroSCORE II, were more symptomatic, and had more complex valve pathology and tricuspid regurgitation resulting in more valve replacements and tricuspid repairs. Intensive and hospital stays were longer. In-hospital deaths (n = 3, all women) were comparable, with more atrial fibrillation in women. The median follow-up time was 3.44 (0.008-8.9) years. The ejection fraction, NYHA, and recurrent regurgitation were low and comparable and atrial fibrillation more frequent in women. The calculated 5-year survival and freedom from re-intervention were comparable (p = 0.9 and p = 0.2). Propensity matching compared 101 well-balanced pairs; women still had fewer resections and more atrial fibrillation. During the follow-up, women had a better ejection fraction. The calculated 5-year survival and freedom from re-intervention were comparable (p = 0.3 and p = 0.3). CONCLUSIONS: Despite women being older and sicker, with more complex valve pathology and subsequent replacement, early and mid-term mortality and the need for reoperation were low and comparable before and after propensity matching, which might be the result of the MIV setting combined with our patient-tailored decision-making. We believe that a multidisciplinary heart team approach is crucial to optimize patient outcomes in MIV, and it might also reduce the widely reported increased surgical risk in female patients. Further studies are needed to prove our findings.

Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Early inflammation following acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) affects myocardial infarct (MI) size and left ventricular remodeling. The mammalian target of rapamycin (mTOR) is involved in the enhanced inflammatory response and its inhibition has exerted beneficial effects on MI size in preclinical models of acute MI. OBJECTIVES: The CLEVER-ACS (Controlled Level Everolimus in Acute Coronary Syndromes) trial evaluated the effects of targeting inflammation by mTOR inhibition in patients with STEMI undergoing PCI. METHODS: CLEVER-ACS was a randomized, multicenter, international, double-blind, placebo-controlled trial. A total of 150 patients with STEMI undergoing PCI were randomly assigned to oral everolimus (days 1-3: 7.5 mg daily; days 4-5: 5.0 mg daily) or placebo for 5 days. The primary endpoint was the change in MI size. The secondary endpoint was the change in microvascular obstruction (MVO) from baseline (12 hours to 5 days after PCI) to 30 days as assessed by cardiac magnetic resonance imaging. RESULTS: The changes in MI size from baseline to 30 days, the primary endpoint, were -14.2 g (95% CI: -17.4 to -11.1 g) and -12.3 g (95% CI: -16.0 to -8.7 g) in the everolimus and placebo groups (P = 0.99). Corresponding changes in MVO were -4.8 g (95% CI: -6.7 to -2.9 g) and -6.3 g (95% CI: -8.7 to -4.0 g) in the everolimus and placebo groups (P = 0.14). Adverse events did not differ between the study groups. CONCLUSIONS: Among STEMI patients undergoing PCI, early mTOR inhibition with everolimus did not reduce MI size or MVO at 30 days. (CLEVER-ACS [Controlled Level Everolimus in Acute Coronary Syndromes; NCT01529554).

Case report of successful low-dose, ultra-slow infusion thrombolysis of prosthetic mitral valve thrombosis in a high risk patient after redo-mitral valve replacement.

BACKGROUND: An increase in transvalvular pressure gradient of prosthetic valve should always raise suspicion for obstructive valve thrombosis. A multimodality diagnostic approach including transthoracic echocardiography, transoesophageal echocardiography (TOE), cinefluoroscopy, or computed tomography (CT) is necessary for a prompt diagnosis. The management of mechanical prosthetic valve thrombosis (PVT) is high risk in any therapeutic option taken. Emergency valve replacement is recommended for critically ill patients. Fibrinolysis is an alternative for patients with contraindication to surgery or if surgery is not immediately available. CASE SUMMARY: A 52-year-old woman presented with symptoms and signs of cardiac congestion. On laboratory, brain natriuretic peptide was elevated and international normalized ratio (INR) was in subtherapeutic range. She underwent a mitral valve replacement with mechanical prosthesis 7 months before, because of a significant residual regurgitation after repair on the same year. TOE revealed severe stenosis of the prosthesis with immobile anterior disc but there was no mass present. CT revealed a minor lesion at the hinge points of the prosthesis without involvement of the ring, suggestive for thrombus. The initial fruitless management with intravenous (i.v) heparin in high therapeutic range was followed by a successful 'low-dose, ultra-slow' fibrinolysis. DISCUSSION: CT may help differentiate thrombus vs. pannus. The acute onset of symptoms, inadequate anticoagulation, and restricted leaflet motion increased the suspicion for PVT. The current European guidelines propose normal dose fibrinolysis. We performed 'low-dose, ultra-slow' fibrinolysis due to lower bleeding risk with successful results. Low dose should be considered as alternative to normal dose fibrinolysis or urgent surgery.

Novel Magnetic Resonance Late Gadolinium Enhancement With Fixed Short Inversion Time in Ischemic Myocardial Scars.

AIMS: Late gadolinium enhancement (LGE) visualizes scar tissue after myocardial infarction. However, in clinically used LGE sequences, subendocardial infarcts can be missed due to low contrast between blood pool and subendocardium. The purpose of his study was to compare scar visibility in a novel 3-dimensional (3D) single breath-hold inversion recovery sequence with fixed, short inversion time (TI = 100 milliseconds) (short LGE) and standard 3D LGE imaging with individually adjusted TI (LGE). METHODS: Short LGE and LGE (both sequences with the same settings: spatial resolution, 1.2 × 1.2 mm; slice thickness, 8 mm; field of view, 350 × 350 mm; single breath-hold) were acquired in 64 patients with previous MI (13 female; mean age, 57 ± 19 years) at 1.5 T. Inversion time was set to 100 milliseconds in short LGE and adjusted individually in LGE according to the Look-Locker sequence. Two independent readers evaluated 1088 segments (17-segment model), identified infarcted segments, and categorized scar visibility (5 = excellent, 1 = poor scar visibility) and scar transmurality (4 = transmural, 0 = no scar) using a 5-point Likert scale. Signal intensity ratios between short LGE and LGE for scar and blood pool, for scar and remote myocardium, and for remote myocardium and blood pool were calculated. RESULTS: Short LGE showed 197 infarcted segments out of 1088 (18.1%); LGE revealed 191 segments (17.6%). Short LGE with dark scar and bright blood pool demonstrated better overall scar visibility, especially in subendocardially infarcted segments compared with LGE (4.2 vs 3.0, 5 = excellent visibility; P = 0.01). Signal intensity ratios for short LGE relative to LGE were 1.42 for scar/blood pool, 0.8 for scar/remote myocardium, and 0.22 for remote myocardium/blood.Overall transmurality was not rated higher in short LGE compared with LGE (P = 0.8). More fibrous tissue and total fibrous percentage (P = 0.04) were measured in short LGE compared with LGE, whereas myocardial mass was not significantly different (P = 0.5). Acquisition time was similar between short LGE and LGE (26 ± 4 seconds vs 25 ± 9 seconds, P = 0.7). CONCLUSIONS: Short LGE is a fast, single breath-hold 3D LGE sequence with no need for myocardial nulling due to fixed inversion time with improved scar visibility, especially in subendocardial infarcts.

Tricuspid Regurgitation: Predicting the Need for Intervention, Procedural Success, and Recurrence of Disease.

Interest in tricuspid valve pathology has rapidly expanded in response to reported poor clinical outcome for functional tricuspid regurgitation and the limited indications and options for treatment. In the past few years, different transcatheter technologies have emerged as alternatives to conventional surgery to serve this untreated high-risk population. In this review, the authors explore the indications for intervention in tricuspid regurgitation according to current guidelines, the published research to support the expansion of these indications including the role of transcatheter interventions, and the risk factors for therapy failure, which may help define the appropriate patient population for treatment.