Hemodynamic Assessment in Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology. OBJECTIVES: This study analyzed altered cardiac hemodynamics during TTS to elucidate underlying disease mechanisms. METHODS: Left ventricular (LV) pressure-volume loops were recorded in 24 consecutive patients with TTS and a control population of 20 participants without cardiovascular diseases. RESULTS: TTS was associated with impaired LV contractility (end-systolic elastance 1.74 mm Hg/mL vs 2.35 mm Hg/mL [P = 0.024]; maximal rate of change in systolic pressure over time 1,533 mm Hg/s vs 1,763 mm Hg/s [P = 0.031]; end-systolic volume at a pressure of 150 mm Hg, 77.3 mL vs 46.4 mL [P = 0.002]); and a shortened systolic period (286 ms vs 343 ms [P < 0.001]). In response, the pressure-volume diagram was shifted rightward with significantly increased LV end-diastolic (P = 0.031) and end-systolic (P < 0.001) volumes, which preserved LV stroke volume (P = 0.370) despite a lower LV ejection fraction (P < 0.001). Diastolic function was characterized by prolonged active relaxation (relaxation constant 69.5 ms vs 45.9 ms [P < 0.001]; minimal rate of change in diastolic pressure -1,457 mm Hg/s vs -2,192 mm Hg/s [P < 0.001]), whereas diastolic stiffness (1/compliance) was not affected during TTS (end-diastolic volume at a pressure of 15 mm Hg, 96.7 mL vs 109.0 mL [P = 0.942]). Mechanical efficiency was significantly reduced in TTS (P < 0.001) considering reduced stroke work (P = 0.001), increased potential energy (P = 0.036), and a similar total pressure-volume area compared with that of control subjects (P = 0.357). CONCLUSIONS: TTS is characterized by reduced cardiac contractility, a shortened systolic period, inefficient energetics, and prolonged active relaxation but unaltered diastolic passive stiffness. These findings may suggest decreased phosphorylation of myofilament proteins, which represents a potential therapeutic target in TTS. (Optimized Characterization of Takotsubo Syndrome by Obtaining Pressure Volume Loops [OCTOPUS]; NCT03726528).

Effect of allogeneic adipose tissue-derived mesenchymal stromal cell treatment in chronic ischaemic heart failure with reduced ejection fraction - the SCIENCE trial.

AIMS: The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: The study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II-III, left ventricular ejection fraction (LVEF) <45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels >300 pg/ml. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6-month follow-up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac-related adverse events during a 3-year follow-up period. There were no significant differences between groups during follow-up in LVESV (0.3 ± 5.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end-diastolic volume (-2.0 ± 6.0 ml, p = 0.736) and LVEF (-1.6 ± 1.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-min walk test, NT-proBNP, C-reactive protein or quality of life the first year in any groups. CONCLUSION: The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre-defined endpoints and induce restoration of cardiac function or clinical symptoms.

Atrial Giant Cell Myocarditis as a Cause of Heart Failure: Diagnostic Pathway and Successful Treatment.

We present a patient with acute heart failure and new onset atrial fibrillation secondary to giant cell myocarditis with lone atrial involvement. The diagnosis was managed with cardiac magnetic resonance and confirmed by interventionally guided biopsy. In the future, diagnosis could be managed noninvasively for this rare entity as the gold standard. (Level of Difficulty: Advanced.).

The ALSTER-TAVI All-Comers Registry: Procedural and 1-Year Clinical Outcomes of Balloon-Expandable vs Self-Expanding Contemporary TAVI Valves.

OBJECTIVES: Both balloon-expandable and self-expanding transcatheter aortic valves are used for transcatheter aortic valve implantation (TAVI). We compared procedural and clinical outcome variables of Sapien 3 and Evolut R/Pro in an all-comers collective. METHODS: In this single-center registry, patients were consecutively treated with the Sapien 3 from November 2014 to March 2017 (n = 129) and from April 2017 to December 2018 mainly (>95%) with the Evolut R/Pro (n = 124), due to a switch in the main TAVI supplier driven by hospital management. Data were retrospectively analyzed before and after the switch. RESULTS: One-year follow-up data were available for 122 (94%) of the Sapien and 112 (90%) of the Evolut patients. Baseline characteristics were comparable (EuroSCORE: Sapien 21.8 ± 0.9% vs Evolut 22.5 ± 0.8%; P=.20). Evolut implantation was associated with a higher radiation dose (Sapien 35770 ± 2345 mGy•cm² vs Evolut 85072 ± 8202 mGy•cm²; P<.001), more postimplantation balloon dilations (Sapien 17.1% vs Evolut 37.1%; P<.001), but similar procedure time (Sapien 75.2 ± 3.8 min vs Evolut 74.6 ± 3 min; P=.30). In-hospital mortality (Sapien 3.1% vs Evolut 4.0%; P=.70), all-cause mortality (Sapien 13.2% vs Evolut 15.3%; P=.70), all-stroke rate (Sapien 1.5% vs Evolut 6.5%; P=.05), and pacemaker implantation rate (Sapien 13.2% vs Evolut 18.5%; P=.30) were similar at 1 year. Permanent pacemaker rate was numerically higher in the first 6 months with Evolut (<6 months 26.7% vs >6 months 16%; P=.62); furthermore, radiation dose and balloon dilations also suggest a learning curve with Evolut. CONCLUSIONS: Switching from Sapien 3 to Evolut R/Pro was not associated with a difference regarding periprocedural or 1-year clinical outcomes.

Rationale and design of the European multicentre study on Stem Cell therapy in IschEmic Non-treatable Cardiac diseasE (SCIENCE).

AIMS: Ischaemic heart failure (IHF) patients have a poor prognosis even with current guideline-derived therapy. Intramyocardial injections of autologous or allogeneic mesenchymal stromal cells might improve cardiac function leading to better clinical outcome. METHODS: The SCIENCE (Stem Cell therapy in IschEmic Non-treatable Cardiac diseasE) consortium has initiated a Horizon 2020 funded multicentre phase II study in six European countries. It is a double-blind, placebo-controlled trial testing the safety and efficacy of allogeneic Cardiology Stem Cell Centre Adipose-derived Stromal Cells (CSCC_ASC) from healthy donors or placebo in 138 symptomatic IHF patients. Main inclusion criteria are New York Heart Association class II-III, left ventricular ejection fraction < 45% and N-terminal pro-B-type natriuretic peptide levels > 300 pg/mL. Patients are randomized in a 2:1 pattern to receive intramyocardial injections of either CSCC_ASC or placebo. CSCC_ASC and placebo treatments are prepared centralized at Rigshospitalet in 5 mL vials as an off-the-shelf product. Vials are distributed to all clinical partners and stored in nitrogen vapour tanks ready to be used directly after thawing. A total of 100 × 106 CSCC_ASC or placebo are injected directly into viable myocardium in the infarct border zone using the NOGA XP system (BDS, Cordis, Johnson & Johnson, USA). Primary endpoint is a centralized core-laboratory assessed change in left ventricular end-systolic volume at 6-month follow-up measured by echocardiography. The trial started in January 2017, 58 patients were included and treated until July 2018. CONCLUSION: The SCIENCE trial will provide clinical data on efficacy and safety of intramyocardial cell therapy of allogeneic adipose-derived stromal cells from healthy donors in patients with IHF.