Contemporary guideline-directed medical therapy in de novo, chronic, and worsening heart failure patients: First data from the TITRATE-HF study.

AIMS: Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. METHODS AND RESULTS: TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. CONCLUSION: This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.

Synergistic action of atrial dilation and sodium channel blockade on conduction in rabbit atria.

INTRODUCTION: The aim of this study was to investigate the interaction of atrial dilation and blockade of the rapid sodium channel on atrial conduction and degree of anisotropy. METHODS AND RESULTS: The right atrium was acutely dilated by increasing intra-atrial pressure from 2 to 9 cm H2O in 14 isolated rabbit hearts. A rectangular mapping array of 240 electrodes (spatial resolution 0.5 mm) was positioned on the free wall of the right atrium during pacing from four different directions at intervals of 240 and 140 msec. In nondilated atria, 0.5 and 1.0 mg/L of the use-dependent INa blocker flecainide prolonged the total conduction time under the mapping electrode by 15% to 75%. In dilated atria, flecainide depressed conduction by 24% to 89% (P < 0.05). The incidence of intra-atrial conduction block increased from 0.6%-0.8% to 3.3%-7.2% in nondilated atria and from 3.9%-4.6% to 13%-21% in dilated atria (P < 0.05). The direction of activation relative to the crista terminalis and major pectinate muscles was of major importance for occurrence of conduction block. During rapid pacing, the degree of anisotropy in conduction increased by the combination of atrial dilation and flecainide (1.0 mg/L) from 1.7 +/- 0.1 to 2.2 +/- 0.4 (P < 0.05). The effects of dilation and flecainide on conduction were clearly synergistic. The effect of flecainide on the atrial refractory period also was enhanced by atrial dilation. CONCLUSION: In dilated atria, blockade of the rapid sodium channels caused a higher degree of local conduction delay and intra-atrial conduction block than in nondilated atria.

Effects of acute atrial dilation on heterogeneity in conduction in the isolated rabbit heart.

INTRODUCTION: Atrial dilation plays an important role in the development and persistence of atrial fibrillation (AF). The mechanisms by which atrial dilation increases the vulnerability to AF are not fully understood. METHODS AND RESULTS: In 11 isolated rabbit hearts, the right atrium was acutely dilated by increasing the intra-atrial pressure from 2 to 9 and 14 cm H2O. A rectangular mapping array of 240 electrodes (spatial resolution 0.5 mm) was positioned on the free wall of the right atrium. The atrium was paced from four different sites at intervals of 240 and 125 msec. At normal atrial pressure (2 cm H2O), conduction was uniform in all directions with an anisotropy ratio between 1.5 and 1.7. Increasing the pressure to 9 cm H2O decreased the normalized conduction velocity during rapid pacing by 18%. The incidence of areas of slow conduction and conduction block increased from 6.6% and 1.6% to 10.2% and 3.3%. At 14 cm H2O, conduction velocity decreased by 31% and the percentage of slow conduction and block further increased to 11.5% and 6.6% (P < 0.001). The appearance of lines of intra-atrial block was largely dependent on the pacing site. Whereas during pacing at the cranial part of the crista terminalis no increase in conduction delays occurred, pacing from the low right atrium unmasked several lines of block oriented parallel to the major trabeculae and the crista terminalis. In an additional series of six hearts the left atrium also was mapped. The effect of dilation of the left atrium was comparable to that of the right atrium. Increasing the atrial pressure to 14 cm H2O increased the amount of intra-atrial conduction block threefold to fourfold. CONCLUSION: Acute atrial dilation results in slowing of conduction and an increase of the amount of intra-atrial conduction block. The increase in spatial heterogeneity in conduction was related to the anisotropic properties of the atrial wall.