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.

Shorter RSPV cryoapplications result in less phrenic nerve injury and similar 1-year freedom from atrial fibrillation.

BACKGROUND: In the 123-study, we prospectively assessed, in a randomized fashion, the minimal cryoballoon application time necessary to achieve pulmonary vein (PV) isolation (PVI) in patients with paroxysmal atrial fibrillation (AF) with the aim to reduce complications by shortening the application duration. The first results of this study demonstrated that shortened cryoballoon applications (<2 minutes) resulted in less phrenic nerve injury (PNI) without compromising acute isolation efficacy for the right PVs. We now report the 1-year follow-up results regarding safety and efficacy of shorter cryoballoon applications. METHODS: A total of 222 patients with AF were randomized to two applications of 1 min "short," 2 min "medium," or 3 min "long" duration, 74 per group. Recurrence of AF and PV reconduction at 1-year follow-up were assessed. RESULTS: The overall 1-year freedom from AF was 79% and did not differ significantly between the short, medium, and long application groups (77%, 74%, and 85% for short, medium, and long application groups, respectively; P = 0.07). In 30 patients, a redo PVI procedure was performed. For all four PVs, there was no significant difference in reconduction between the three groups. Reconduction was most common in the left superior PV (57%). The right superior PV (RSPV) showed significantly less reconduction (17%) compared to the other PVs. CONCLUSIONS: Shortening cryoballoon applications of the RSPV to <2 minutes results in less PNI, while acute success and 1-year freedom from AF are not compromised. Therefore, shorter cryoballoon applications (especially) in the RSPV could be used to reduce PNI.

Predicting Early Mortality Among Implantable Defibrillator Patients Treated With Cardiac Resynchronization Therapy.

BACKGROUND: The beneficial effects of a cardiac resynchronization defibrillator (CRT-D) in patients with heart failure, low left ventricular ejection fraction (LVEF), and wide QRS have clearly been established. Nevertheless, mortality remains high in some patients. The aim of this study was to develop and validate a risk score to identify patients at high risk for early mortality who are implanted with a CRT-D. METHODS AND RESULTS: For predictive modelling, 1282 consecutive patients from 5 centers (74% male; median age 66 years; median LVEF 25%; New York Heart Association class III-IV 60%; median QRS-width 160 ms) were randomly divided into a derivation and validation cohort. The primary endpoint is mortality at 3 years. Model development was performed using multivariate logistic regression by checking log likelihood, Akaike information criterion, and Bayesian information criterion. Model performance was validated using C statistics and calibration plots. The risk score included 7 independent mortality predictors, including myocardial infarction, LVEF, QRS duration, chronic obstructive pulmonary disease, chronic kidney disease, hyponatremia, and anemia. Calibration-in-the-large was suboptimal, reflected by a lower observed mortality (44%) than predicted (50%). The validated C statistic was 0.71 indicating modest performance. CONCLUSION: A risk score based on routine, readily available clinical variables can assist in identifying patients at high risk for early mortality within 3 years after CRT-D implantation.

Shorter cryoballoon applications times do effect efficacy but result in less phrenic nerve injury: Results of the randomized 123 study.

BACKGROUND: The second-generation cryoballoon significantly improves outcome of pulmonary vein isolation (PVI) but may cause more complications than the first generation. Currently, no consensus regarding optimal cryoballoon application time exists. The 123-study aimed to assess the minimal cryoballoon application duration necessary to achieve PVI (primary endpoint) and the effect of application duration on prevention of phrenic nerve injury (PNI). METHODS: Patients <75 years of age with paroxysmal atrial fibrillation, normal PV anatomy, and left atrial size <40 cc/m² or <50 mm were randomized to two applications of different duration: "short," "medium," or "long." A total of 222 patients were enrolled, 74 per group. RESULTS: Duration per application was 105 (101-108), 164 (160-168), and 224 (219-226) s and isolation was achieved in 79, 89, and 90% (P < 0.001) of the PVs after two applications in groups short, medium, and long, respectively. Only for the left PVs, the success rate of the short group was significantly less compared to the medium- and long-duration groups (P < 0.001). PNI during the procedure occurred in 19 PVs (6.5%) in the medium and in 20 PVs (6.8%) in the long duration groups compared to only five PVs (1.7%) in the short duration group (P < 0.001). CONCLUSIONS: Short cryoballoon ablation application times, less than 2 min, did affect the success for the left PVs but not for the right PVs and resulted in less PNI. A PV tailored approach with shorter application times for the right PVs might be advocated.

Single-centre experience of 85 patients with a continuous-flow left ventricular assist device: clinical practice and outcome after extended support.

OBJECTIVES: We evaluated our single-centre clinical experience with the HeartMate II (HM II) left ventricular assist device (LVAD) as a bridge to transplantation (BTT) in end-stage heart failure (HF) patients. METHODS: Survival rates, echocardiographic parameters, laboratory values and adverse events of 85 consecutive patients supported with a HM II were evaluated. RESULTS: Overall, mean age was 45 ± 13 years, 62 (73%) were male and non-ischaemic dilatated cardiomyopathy was present in 60 (71%) patients. The median duration of mechanical support was 387 days (IQR 150-600), with a range of 1-1835 days. The 6-month, 1-, 2-, 3- and 4-year survival rates during HM II LVAD support were 85, 81, 76, 76 and 68%, respectively. Echocardiographic parameters demonstrated effective left ventricular unloading, while laboratory results reflected adequate organ perfusion. However, HM II support was associated with adverse events, such as infections in 42 patients (49%; 0.67 events/patient-year), cardiac arrhythmia in 44 (52%; 0.86 events/patient-year), bleeding complications in 32 (38%; 0.43 events/patient-year) and neurological dysfunction in 17 (20%; 0.19 events/patient-year). CONCLUSIONS: In view of the increasing shortage of donor hearts, HM II LVAD support may be considered a life-saving treatment in end-stage HF patients, with good survival. However, it is still associated with some serious adverse events, of which neurological complications are the most critical.

A new electric method for non-invasive continuous monitoring of stroke volume and ventricular volume-time curves.

BACKGROUND: In this paper a new non-invasive, operator-free, continuous ventricular stroke volume monitoring device (Hemodynamic Cardiac Profiler, HCP) is presented, that measures the average stroke volume (SV) for each period of 20 seconds, as well as ventricular volume-time curves for each cardiac cycle, using a new electric method (Ventricular Field Recognition) with six independent electrode pairs distributed over the frontal thoracic skin. In contrast to existing non-invasive electric methods, our method does not use the algorithms of impedance or bioreactance cardiography. Instead, our method is based on specific 2D spatial patterns on the thoracic skin, representing the distribution, over the thorax, of changes in the applied current field caused by cardiac volume changes during the cardiac cycle. Since total heart volume variation during the cardiac cycle is a poor indicator for ventricular stroke volume, our HCP separates atrial filling effects from ventricular filling effects, and retrieves the volume changes of only the ventricles. METHODS: ex-vivo experiments on a post-mortem human heart have been performed to measure the effects of increasing the blood volume inside the ventricles in isolation, leaving the atrial volume invariant (which can not be done in-vivo). These effects have been measured as a specific 2D pattern of voltage changes on the thoracic skin. Furthermore, a working prototype of the HCP has been developed that uses these ex-vivo results in an algorithm to decompose voltage changes, that were measured in-vivo by the HCP on the thoracic skin of a human volunteer, into an atrial component and a ventricular component, in almost real-time (with a delay of maximally 39 seconds). The HCP prototype has been tested in-vivo on 7 human volunteers, using G-suit inflation and deflation to provoke stroke volume changes, and LVot Doppler as a reference technique. RESULTS: The ex-vivo measurements showed that ventricular filling caused a pattern over the thorax quite distinct from that of atrial filling. The in-vivo tests of the HCP with LVot Doppler resulted in a Pearson's correlation of R = 0.892, and Bland-Altman plotting of SV yielded a mean bias of -1.6 ml and 2SD =14.8 ml. CONCLUSIONS: The results indicate that the HCP was able to track the changes in ventricular stroke volume reliably. Furthermore, the HCP produced ventricular volume-time curves that were consistent with the literature, and may be a diagnostic tool as well.

The ECG in cardiac resynchronization therapy: influence of left and right ventricular preactivation and relation to acute response.

INTRODUCTION: The aims of this study were to compare ECG signs of biventricular electrical resynchronization during cardiac resynchronization therapy (CRT) with various interventricular (VV) delays and to correlate these and other ECG characteristics with the acute hemodynamic benefit of CRT. METHODS AND RESULTS: Thirty-four patients with heart failure and a left bundle branch block (LBBB) pattern were prospectively enrolled. A 12-lead surface ECG and the relative improvement in left ventricular (LV) dP/dt(max) (the maximum rate of pressure rise) were recorded at baseline and during CRT with VV delays varying from 80 ms LV preactivation to 40 ms right ventricular (RV) preactivation. Rightward QRS-axis shift occurred in 71-80% among all VV delays. Activation reversal to dominant negative in leads I/aVL was progressively observed at increasing LV preactivation (53-65%) and less (18-22%) during RV preactivation. Activation reversal to dominant positive in leads V1/V2 was observed in 21-27% during LV preactivation and in 6-15% during RV preactivation. Higher acute response to CRT was independently predicted by a complete LBBB at baseline (regression coefficient B = 7.7 [0.3-15.0], P = 0.042), later timing of LV depolarization within the QRS at baseline (Q-LVsense: B = 0.2 [0.1-0.3], P = 0.002), and biventricular electrical resynchronization during CRT as evidenced by activation reversal in leads I/aVL (B = 9.9 [3.2-16.6], P = 0.005). CONCLUSION: ECG signs of biventricular electrical resynchronization are present over a wide range of LV preactivated VV delays but to a lesser extent during RV preactivation. The presence of complete LBBB and longer Q-LVsense at baseline and signs of biventricular electrical resynchronization during CRT predict higher acute hemodynamic response.