Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).

Patient Characteristics, Outcomes, and Effects of Dapagliflozin According to the Duration of Heart Failure: A Prespecified Analysis of the DELIVER Trial.

BACKGROUND: How patient characteristics and outcomes vary according to the duration of heart failure (HF) is unknown in individuals with mildly reduced or preserved ejection fraction. We compared these, and the efficacy and safety of dapagliflozin, according to the time from diagnosis of HF in a prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure). METHODS: HF duration was categorized as ≤6 months, >6 to 12 months, >1 to 2 years, >2 to 5 years, or >5 years. The primary outcome was the composite of worsening HF or cardiovascular death. The effect of treatment was examined by HF duration category. RESULTS: The number of patients in each category was as follows: 1160 (≤6 months), 842 (>6 to 12 months), 995 (>1 to 2 years), 1569 (>2 to 5 years), and 1692 (>5 years). Patients with longer-duration HF were older and had more comorbidities with worse symptoms. The rate of the primary outcome (per 100 person-years) increased with HF duration: ≤6 months, 7.3 (95% CI, 6.3 to 8.4); >6 to 12 months, 7.1 (6.0 to 8.5); >1 to 2 years, 8.4 (7.2 to 9.7); >2 to 5 years, 8.9 (7.9 to 9.9); and >5 years, 10.6 (9.5 to 11.7). Similar trends were seen for other outcomes. The benefit of dapagliflozin was consistent across HF duration category: the hazard ratio for the primary outcome in the ≤6-month group was 0.67 (95% CI, 0.50 to 0.91); >6 to 12 months, 0.78 (0.55 to 1.12); >1 to 2 years, 0.81 (0.60 to 1.09); >2 to 5 years, 0.97 (0.77 to 1.22); and >5 years, 0.78 (0.64 to 0.96; Pinteraction=0.41). The absolute benefit was greatest in longest-duration HF; the number needed to treat for HF >5 years was 24 versus 32 for ≤6 months. CONCLUSIONS: Patients with longer-duration HF were older, had more comorbidities and symptoms, and had higher rates of worsening HF and death. The benefits of dapagliflozin were consistent across HF duration. Even patients with long-standing HF and generally mild symptoms are not stable, and it is not too late for such patients to benefit from a sodium-glucose cotransporter 2 inhibitor. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03619213.

Remote haemodynamic monitoring of pulmonary artery pressures in patients with chronic heart failure (MONITOR-HF): a randomised clinical trial.

BACKGROUND: The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system. METHODS: MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible patients had chronic heart failure of New York Heart Association class III and a previous heart failure hospitalisation, irrespective of ejection fraction. Patients were randomly assigned (1:1) to haemodynamic monitoring (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA) or standard care. All patients were scheduled to be seen by their clinician at 3 months and 6 months, and every 6 months thereafter, up to 48 months. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. All analyses were by intention-to-treat. This trial was prospectively registered under the clinical trial registration number NTR7673 (NL7430) on the International Clinical Trials Registry Platform. FINDINGS: Between April 1, 2019, and Jan 14, 2022, we randomly assigned 348 patients to either the CardioMEMS-HF group (n=176 [51%]) or the control group (n=172 [49%]). The median age was 69 years (IQR 61-75) and median ejection fraction was 30% (23-40). The difference in mean change in KCCQ overall summary score at 12 months was 7·13 (95% CI 1·51-12·75; p=0·013) between groups (+7·05 in the CardioMEMS group, p=0·0014, and -0·08 in the standard care group, p=0·97). In the responder analysis, the odds ratio (OR) of an improvement of at least 5 points in KCCQ overall summary score was OR 1·69 (95% CI 1·01-2·83; p=0·046) and the OR of a deterioration of at least 5 points was 0·45 (0·26-0·77; p=0·0035) in the CardioMEMS-HF group compared with in the standard care group. The freedom of device-related or system-related complications and sensor failure were 97·7% and 98·8%, respectively. INTERPRETATION: Haemodynamic monitoring substantially improved quality of life and reduced heart failure hospitalisations in patients with moderate-to-severe heart failure treated according to contemporary guidelines. These findings contribute to the aggregate evidence for this technology and might have implications for guideline recommendations and implementation of remote pulmonary artery pressure monitoring. FUNDING: The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories.

The jugular approach for leadless pacing: A novel and safe alternative.

AIMS: To evaluate safety of leadless pacemaker implantation through the internal jugular vein in a larger cohort with longer follow-up. Moreover, feasibility of non-apical pacing as well as relation between pacing site and QRS duration were assessed. METHODS: Eighty Two consecutive patients, who received a leadless pacemaker though the internal jugular vein, were included. Electrical parameters were measured at regular follow-up and any complications were registered. Paced QRS interval was compared for three pacing sites, RVOT, RV mid septum, and RV apical septum. RESULTS: In all patients, the leadless pacemaker was implanted successfully. In 69 patients, the device was implanted in a non-apical position. In 71% of cases, the device could be deployed at first attempt. The median fluoroscopy time was 4.4 min (range 0.9-51) The paced QRS interval was significantly narrower for non-apical pacing sites compared to apical pacing si 156  vs. 179 ms. p = .04, respectively. During mean follow-up of 16 months (range 0-43 months), electrical parameters remained stable. Two complications occurred, which could be resolved during the implant procedure. There were no access site related complications. CONCLUSION: The jugular approach for leadless pacemaker implantation is feasible and may avoid vascular complications. It facilitates non-apical positioning of leadless pacemakers leading to a narrower paced QRS interval. The jugular approach allows for immediate post procedural ambulation.

Leadless pacing: Going for the jugular.

BACKGROUND: Leadless pacing is generally performed from a femoral approach. However, the femoral route is not always available. Until now, data regarding implantation using a jugular approach other than a single-case report were lacking. METHODS: The case records of all patients who underwent internal jugular venous (IJV) leadless pacemaker implantation (Micra, Medtronic, Dublin, Ireland) at our center were analyzed retrospectively. RESULTS: Nineteen patients underwent IJV leadless pacemaker implantation, nine females, mean age of 77.5 ±9.6  years; permanent atrial fibrillation in all patients with normal left ventricular ejection fraction. Implant indication was atrioventricular conduction disturbance in 10, pre-AV node ablation in seven, and replacement of a conventional VVI pacemaker in two (infection in one and lead malfunction in the other). The device was positioned at the superior septum in seven patients, apicoseptal in seven patients, and midseptal in five patients. In 12 patients, a sufficient device position was obtained at the first attempt, in three at the second, in one at the third, in one at the fourth, and in two at the sixth attempt. The mean pacing threshold was 0.56 ± 0.39V at 0.24-ms pulse width, sensed amplitude was 9.1 ± 3.2 mV, mean fluoroscopy duration was 3.1 ± 1.6 min. There were no vascular or other complications. At follow-up, electrical parameters remained stable in 18 of 19 patients. CONCLUSION: Although experience is minimal, we suggest that the IJV approach is safe and may be considered in patients where the femoral approach is contraindicated.

Mortality differences in acute myocardial infarction patients in the Netherlands: The weekend-effect.

Objective: Several studies have shown that patients admitted with an acute myocardial infarction during the weekends have a higher mortality rate than those admitted during weekdays, possibly attributable to less trained personnel available and a lower use of medical procedures. The current study aimed to assess this 'weekend-effect' in a nationwide registry. Methods: In the Netherlands, all inhabitants are, by law, obliged to have health insurance and all claim data are centrally registered. In 2012 and 2013, all national diagnose-codings of STEMI and NSTEMI patients were acquired. One-year mortality rates and treatment with percutaneous coronary intervention (PCI) were compared between weekdays and weekends (holidays included). Results: In total, 59,534 patients (67 ± 13 years, 39,545(66%) male) were included of whom 33,904(57%) had a NSTEMI. Overall 6857(12%) patients died in the year following the acute myocardial infarction registration. In STEMI patients, no differences in one-year mortality rates were observed between admission on weekdays or weekends. In NSTEMI patients, one-year mortality was higher in those admitted during weekends (weekdays 11% versus weekends 13%, P < .001). Furthermore, STEMI patients admitted during weekends were more often treated with PCI (weekdays 77% versus weekends 81%, P < .001). Conversely, NSTEMI patients admitted during weekends were less often treated with PCI (weekdays 35% versus weekends 32%, P < .001). Conclusion: Differences in treatment and mortality rates exist between acute myocardial infarction patients admitted during weekdays and weekends. NSTEMI patients admitted during weekends are less often treated with PCI and have a higher mortality rate than patients admitted during weekdays.

Application and comparison of the FADES, MADIT, and SHFM-D risk models for risk stratification of prophylactic implantable cardioverter-defibrillator treatment.

AIMS: Implantable cardioverter-defibrillator (ICD) treatment is beneficial in selected patients. However, it remains difficult to accurately predict which patients benefit most from ICD implantation. For this purpose, different risk models have been developed. The aim was to validate and compare the FADES, MADIT, and SHFM-D models. METHODS AND RESULTS: All patients receiving a prophylactic ICD at the Leiden University Medical Center were evaluated. Individual model performance was evaluated by C-statistics. Model performances were compared using net reclassification improvement (NRI) and integrated differentiation improvement (IDI). The primary endpoint was non-benefit of ICD treatment, defined as mortality without prior ventricular arrhythmias requiring ICD intervention. A total of 1969 patients were included (age 63 ± 11 years; 79% male). During a median follow-up of 4.5 ± 3.9 years, 318 (16%) patients died without prior ICD intervention. All three risk models were predictive for event-free mortality (all: P < 0.001). The C-statistics were 0.66, 0.69, and 0.75, respectively, for FADES, MADIT, and SHFM-D (all: P < 0.001). Application of the SHFM-D resulted in an improved IDI of 4% and NRI of 26% compared with MADIT; IDI improved 11% with the use of SHFM-D instead of FADES (all: P < 0.001), but NRI remained unchanged (P = 0.71). Patients in the highest-risk category of the MADIT and SHFM-D models had 1.7 times higher risk to experience ICD non-benefit than receive appropriate ICD interventions [MADIT: mean difference (MD) 20% (95% CI: 7-33%), P = 0.001; SHFM-D: MD 16% (95% CI: 5-27%), P = 0.005]. Patients in the highest-risk category of FADES were as likely to experience ICD intervention as ICD non-benefit [MD 3% (95% CI: -8 to 14%), P = 0.60]. CONCLUSION: The predictive and discriminatory value of SHFM-D to predict non-benefit of ICD treatment is superior to FADES and MADIT in patients receiving prophylactic ICD treatment.

Prognostic Impact of Implementation of QRS Characteristics in the Seattle Heart Failure Model in ICD and CRT-D Recipients.

BACKGROUND: The Seattle Heart Failure Model (SHFM) provides accurate estimates of survival in heart failure (HF) patients. The model is, however, not developed for HF patients with cardiac resynchronization therapy (CRT). The aim of this study was to assess the prognostic value of SHFM combined with QRS morphology and CRT-related change in QRS duration in implantable cardioverter defibrillator (ICD) and CRT defibrillator (CRT-D) recipients. METHODS: All patients who underwent prophylactic ICD implantation at the Leiden University Medical Center since 1996 were included. Baseline SHFM, QRS morphology, and duration before and after device implantation were determined. The regression coefficients of the QRS characteristics derived from a Cox regression analysis were implemented in the SHFM. SHFM-estimated survival was compared with Kaplan-Meier observed survival. RESULTS: The current study includes 1,834 defibrillator recipients (63 ± 11 years; 79% male; 53% CRT-D). In 585 (60%) CRT-D recipients a left bundle branch block was present, the mean QRS duration was 147 ± 31 ms before and 151 ± 27 ms after device implantation. After a median follow-up of 4.4 years (25(th) -75(th) percentile 2.7-6.4 years), 285 (29%) CRT-D recipients had died. CRT-related decrease in QRS duration adjusted for QRS morphology was associated with improved survival (hazard ratio 1.05/10 ms; 95% confidence interval [CI]: 1.01-1.09; P = 0.02). The estimated 5-year survival of CRT-D recipients after implementation of the QRS characteristic was 70%, and comparable with the observed 5-year survival of 68% (95% CI: 65-72). CONCLUSION: Implementation of native QRS morphology and change in QRS duration due to CRT in the SHFM improves the prognostic value of this model in HF patients with CRT-D.

Cost-effectiveness of primary prevention implantable cardioverter defibrillator treatment: data from a large clinical registry.

BACKGROUND: Although randomized trials have shown the beneficial effect on survival of an implantable cardioverter defibrillator (ICD) as primary prevention therapy in selected patients, data concerning the cost-effectiveness in routine clinical practice remain scarce. Accordingly, the purpose of this study was to assess the cost-effectiveness of primary prevention ICD implantation in the real world. METHODS: Patients receiving primary prevention single-chamber or dual-chamber ICD implantation at the Leiden University Medical Center were included in the study. Using a Markov model, lifetime cost, life years (LYs), and gained quality-adjusted life years (QALYs) were estimated for device recipients and control patients. Data on mortality, complication rates, and device longevity were retrieved from our center and entered into the Markov model. To account for model assumptions, one-way deterministic and probabilistic sensitivity analyses were performed. Importantly, calculations for the estimated incremental cost-effectiveness rate (ICER) per QALY gained are based on several numbers of assumptions, and accordingly findings may have over- or underestimated the cost-effectiveness of ICD therapy. RESULTS: Primary prevention ICD implantation adds an estimated mean of 2.07 LYs and 1.73 QALYs. Increased lifetime cost for single-chamber and dual-chamber ICD recipients were estimated at €60,788 and €64,216, respectively. This resulted for single-chamber ICD recipients, in an estimated ICER of €35,154 per QALY gained. In dual-chamber ICD recipients, an estimated ICER of €37,111 per QALY gained was calculated. According to the probabilistic sensitivity analysis, estimated cost per QALY gained are €35,837 (95% confidence interval [CI]: €28,368-€44,460) for single-chamber and €37,756 (95% CI: €29,055-€46,050) for dual-chamber ICDs. CONCLUSIONS: On the basis of data and detailed costs, derived from routine clinical practice, ICD therapy in selected patients with a reduced left ventricular ejection fraction appears to be cost-effective.

Geographical variation in patient characteristics and outcomes in heart failure with mildly reduced and preserved ejection fraction.

AIMS: Compared to heart failure (HF) with reduced ejection fraction, HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) are increasing in prevalence, yet little is known about the geographic variation in patient characteristics, treatments and outcomes among these two HF phenotypes. The aim of this study was to investigate geographic differences in HFpEF and HFmrEF. METHODS AND RESULTS: We conducted an individual patient analysis of five clinical trials enrolling patients with HFpEF or HFmrEF from North America (NA), Latin America (LA), Western Europe (WE), Central/Eastern Europe and Russia (CEER), and Asia-Pacific (AP). We compared regions using descriptive statistics and multivariable regression models. Among the 19 959 patients included, 4066 (23.1%) had HFmrEF and 15 353 (76.9%) HFpEF. Regardless of HF phenotype, patients from WE were oldest, and those in CEER youngest. LA had the largest portion of females and NA most black patients. Obesity and diabetes were most prevalent in NA and hypertension and coronary heart disease most common in CEER. Self-reported health status varied strikingly and was the worst in NA and best in AP. Among patients with HFmrEF, rates of the primary composite endpoint (cardiovascular death or HF hospitalization) were: NA 12.56 per 100 patient-years (/100py), AP 11.67/100py, CEER 10.12/100py, LA 8.90/100py, and WE 8.43/100py, driven by differences in the rate of HF hospitalization. The corresponding values in HFpEF were 11.47/100py, 7.80/100py, 5.47/100py, 5.92/100py, and 7.80/100py, respectively. CONCLUSIONS: There is substantial geographic variation in patient characteristics, treatment and outcomes among patients with HFpEF and HFmrEF. These findings have implications for interpretation and generalizability of trial results, design and conduct of future trials, and optimization of care for these patients.

Guideline implementation, drug sequencing, and quality of care in heart failure: design and rationale of TITRATE-HF.

AIMS: Current heart failure (HF) guidelines recommend to prescribe four drug classes in patients with HF with reduced ejection fraction (HFrEF). A clear challenge exists to adequately implement guideline-directed medical therapy (GDMT) regarding the sequencing of drugs and timely reaching target dose. It is largely unknown how the paradigm shift from a serial and sequential approach for drug therapy to early parallel application of the four drug classes will be executed in daily clinical practice, as well as the reason clinicians may not adhere to new guidelines. We present the design and rationale for the real-world TITRATE-HF study, which aims to assess sequencing strategies for GDMT initiation, dose titration patterns (order and speed), intolerance for GDMT, barriers for implementation, and long-term outcomes in patients with de novo, chronic, and worsening HF. METHODS AND RESULTS: A total of 4000 patients with HFrEF, HF with mildly reduced ejection fraction, and HF with improved ejection fraction will be enrolled in >40 Dutch centres with a follow-up of at least 3 years. Data collection will include demographics, physical examination and vital parameters, electrocardiogram, laboratory measurements, echocardiogram, medication, and quality of life. Detailed information on titration steps will be collected for the four GDMT drug classes. Information will include date, primary reason for change, and potential intolerances. The primary clinical endpoints are HF-related hospitalizations, HF-related urgent visits with a need for intravenous diuretics, all-cause mortality, and cardiovascular mortality. CONCLUSIONS: TITRATE-HF is a real-world multicentre longitudinal registry that will provide unique information on contemporary GDMT implementation, sequencing strategies (order and speed), and prognosis in de novo, worsening, and chronic HF patients.

Serial cardiac biomarkers, pulmonary artery pressures and traditional parameters of fluid status in relation to prognosis in patients with chronic heart failure: Design and rationale of the BioMEMS study.

AIMS: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms. METHODS: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. CONCLUSION: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively.

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.

Implantable cardioverter-defibrillators have reduced the incidence of resuscitation for out-of-hospital cardiac arrest caused by lethal arrhythmias.

BACKGROUND: Over the last decades, a gradual decrease in ventricular fibrillation (VF) as initial recorded rhythm during resuscitation for out-of-hospital cardiac arrest (OHCA) has been noted. We sought to establish the contribution of implantable cardioverter-defibrillator (ICD) therapy to this decline. METHODS AND RESULTS: Using a prospective database of all OHCA resuscitation in the province North Holland in the Netherlands (Amsterdam Resuscitation Studies [ARREST]), we collected data on all patients in whom resuscitation for OHCA was attempted in 2005-2008. VF OHCA incidence (per 100 000 inhabitants per year) was compared with VF OHCA incidence data during 1995-1997, collected in a similar way. We also collected ICD interrogations of all ICD patients from North Holland and identified all appropriate ICD shocks in 2005-2008; we calculated the number of prevented VF OHCA episodes, considering that only part of the appropriate shocks would result in avoided resuscitation. VF OHCA incidence decreased from 21.1/100 000 in 1995-1997 to 17.4/100 000 in 2005-2008 (P<0.001). Non-VF OHCA increased from 12.2/100 000 to 19.4/100 000 (P<0.001). VF as presenting rhythm declined from 63% to 47%. In 2005-2008, 1972 ICD patients received 977 shocks. Of these shocks, 339 were caused by a life-threatening arrhythmia. We estimate that these 339 shocks have prevented 81 (minimum, 39; maximum, 152) cases of VF OHCA, corresponding with 33% (minimum, 16%; maximum, 63%) of the observed decline in VF OHCA incidence. CONCLUSIONS: The incidence of VF OHCA decreased over the last 10 years in North Holland. ICD therapy explained a decrease of 1.2/100 000 inhabitants per year, corresponding with 33% of the observed decline in VF OHCA.

Association of Dapagliflozin vs Placebo With Individual Kansas City Cardiomyopathy Questionnaire Components in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the DELIVER Trial.

Importance: Dapagliflozin has been shown to improve overall health status based on aggregate summary scores of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. A comprehensive understanding of the responsiveness of individual KCCQ items would allow clinicians to better inform patients on expected changes in daily living with treatment. Objective: To examine the association of dapagliflozin treatment with changes in individual components of the KCCQ. Design, Setting, and Participants: This is a post hoc exploratory analysis of DELIVER, a randomized double-blind placebo-controlled trial conducted at 353 centers in 20 countries from August 2018 to March 2022. KCCQ was administered at randomization and 1, 4, and 8 months. Scores of individual KCCQ components were scaled from 0 to 100. Eligibility criteria included symptomatic HF with left ventricular ejection fraction greater than 40%, elevated natriuretic peptide levels, and evidence of structural heart disease. Data were analyzed from November 2022 to February 2023. Main Outcomes and Measures: Changes in the 23 individual KCCQ components at 8 months. Interventions: Dapagliflozin, 10 mg, once daily or placebo. Results: Baseline KCCQ data were available for 5795 of 6263 randomized patients (92.5%) (mean [SD] age, 71.5 [9.5] years; 3344 male [57.7%] and 2451 female [42.3%]). Dapagliflozin was associated with larger improvements in almost all KCCQ components at 8 months compared with placebo. The most significant improvements with dapagliflozin were observed in frequency of lower limb edema (difference, 3.2; 95% CI, 1.6-4.8; P < .001), sleep limitation by shortness of breath (difference, 3.0; 95% CI, 1.6-4.4; P < .001), and limitation in desired activities by shortness of breath (difference, 2.8; 95% CI, 1.3-4.3; P < .001). Similar treatment patterns were observed in longitudinal analyses integrating data from months 1, 4, and 8. Higher proportions of patients treated with dapagliflozin experienced improvements, and fewer had deteriorations across most individual components. Conclusions and Relevance: In this study of patients with HF with mildly reduced or preserved ejection fraction, dapagliflozin was associated with improvement in a broad range of individual KCCQ components, with the greatest benefits in domains related to symptom frequency and physical limitations. Potential improvements in specific symptoms and activities of daily living might be more readily recognizable and easily communicated to patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03619213.

Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk.

BACKGROUND: Functional mitral regurgitation (MR) is a common finding in heart failure patients with dilated cardiomyopathy and has important prognostic implications. However, the increased operative risk of these patients may result in low referral or high denial rate for mitral valve surgery. Cardiac resynchronization therapy (CRT) has been shown to have a favorable effect on MR. Aims of this study were to (1) evaluate CRT as a therapeutic option in heart failure patients with functional MR and high operative risk and (2) investigate the effect of MR improvement after CRT on prognosis. METHODS AND RESULTS: A total of 98 consecutive patients with moderate-severe functional MR and high operative risk underwent CRT according to current guidelines. Echocardiography was performed at baseline and 6-month follow-up; severity of MR was graded according to a multiparametric approach. Significant improvement of MR was defined as a reduction ≥ 1 grade. All-cause mortality was assessed during follow-up (median 32 [range 6.0 to 116] months). Thirteen patients (13%) died before 6-months follow-up. In the remaining 85 patients, significant reduction in MR was observed in all evaluated parameters. In particular, 42 patients (49%) improved ≥ 1 grade of MR and were considered MR improvers. Survival was superior in MR improvers compared to MR nonimprovers (log rank P<0.001). Mitral regurgitation improvement was an independent prognostic factor for survival (hazard ratio 0.35, confidence interval 0.13 to 0.94; P=0.043). CONCLUSIONS: Cardiac resynchronization therapy is a potential therapeutic option in heart failure patients with moderate-severe functional MR and high risk for surgery. Improvement in MR results in superior survival after CRT.

Relative merits of left ventricular dyssynchrony, left ventricular lead position, and myocardial scar to predict long-term survival of ischemic heart failure patients undergoing cardiac resynchronization therapy.

BACKGROUND: The relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome after cardiac resynchronization therapy remain unknown and were evaluated in the present study. METHODS AND RESULTS: In 397 ischemic heart failure patients, 2-dimensional speckle tracking imaging was performed, with comprehensive assessment of LV radial dyssynchrony, identification of the segment with latest mechanical activation, and detection of myocardial scar in the segment where the LV lead was positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used. Segments with <16.5% radial strain in the region of the LV pacing lead were considered to have extensive myocardial scar (>50% transmurality, validated in a subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position was derived from chest x-ray. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was 133±98 milliseconds. In 271 patients (68%), the LV lead was placed at the latest activated segment (concordant LV lead position), and the mean value of peak radial strain at the targeted segment was 18.9±12.6%. Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995; P=0.001), whereas a discordant LV lead position (hazard ratio, 2.086; P=0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; P<0.001) were independent predictors of worse outcome. Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters. CONCLUSIONS: Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in ischemic heart failure patients treated with cardiac resynchronization therapy. Larger baseline LV dyssynchrony predicted superior long-term survival, whereas discordant LV lead position and myocardial scar predicted worse outcome.

Trans-venous lead removal without the use of extraction sheaths, results of >250 removal procedures.

AIMS: The number of implanted cardiac rhythm devices has rapidly increased in the past decade. Subsequently, the need for lead extraction has also increased. Several techniques of lead removal have been documented from manual traction of the lead to lead extraction assisted with mechanical or laser sheaths. The goal of this study was to review our experience with lead removal using manual traction without the assistance of extraction sheaths. METHODS AND RESULTS: In the Leiden University Medical Center all leads are removed using manual traction without the assistance of extraction sheaths. We have retrospectively reviewed all lead removal procedures performed between 2000 and 2009. Procedures were reviewed for indication, success, complication rates, and mortality. In total, 279 lead removal procedures were included. During these procedures 445 leads were removed. Time since lead implantation: 4.2 ± 4.7 years. During extraction 53(11.9%) leads fractured, of which >50% could still be completely removed using a femoral approach. A longer implantation duration [odds ratio (OR) 1.16 per year, 95% confidence interval (CI) 1.09-1.23] and passive fixation (OR 2.52, 95%CI 1.17-5.45) significantly associated with the chance of lead fracture during lead removal. Clinical success, using the primary approach of manual traction from the pectoral area, was obtained in 228 (84.8%) procedures. Major complications occurred in 2(0.7%) and minor in 13(4.7%) procedures. One patient died within 24 h after the procedure due to septic shock. There was no further mortality within the first month after the procedure. CONCLUSION: Lead removal using manual traction, without the assistance of lead extraction sheaths, is clinically successful in ~85% of the lead extraction procedures. Concomitant morbidity and mortality are low. The highest clinical success (~95%) was observed in patients with leads implanted less than 2.6 years.

Prophylactic implantable cardioverter-defibrillator treatment in the elderly: therapy, adverse events, and survival gain.

AIMS: In elderly patients, obscurity remains regarding the benefit of implantable cardioverter-defibrillator (ICD) treatment as primary prevention of sudden cardiac death. This study assesses implant rates, therapy, adverse events, and survival gain in the elderly primary prevention ICD patient. METHODS AND RESULTS: A total of 1395 patients treated with an ICD for primary prevention of sudden cardiac death at the Leiden University Medical Center were included and allocated to three groups according to age. Endpoints consisted of appropriate shocks and survival gain, defined as the time following first appropriate ICD shock to death. Mean follow-up was 2.9 ± 2.1 years. Fifty-one per cent of the patients were <65 years, 35% were 65-74 years, and 14% were ≥75 years. Prior to the year 2000, no ICDs were implanted in patients ≥75 years; 29% of the ICDs were implanted in patients 65-74 years. After 2005, 53% of the ICD recipients were ≥65 years at the time of implant, including 16% aged ≥75 years (P = 0.03). Five-year cumulative incidence of appropriate shocks was 19% for patients <65 years, 23% for patients 65-74 years, and 13% for patients ≥75 years (P = 0.47). At 1-year following appropriate shock, cumulative incidence for death was 35% for patients ≥75 years as compared with 7% for patients <65 years (P < 0.01). CONCLUSION: In routine clinical practice, the percentage of patients ≥75 years receiving an ICD for primary prevention is increasing. Despite experiencing comparable rates of appropriate ICD shocks, life prolongation by ICD is significantly less in elderly as compared to younger patients.

Update on small-diameter implantable cardioverter-defibrillator leads performance.

BACKGROUND: The performance of small diameter implantable cardioverter defibrillator (ICD) leads is questionable. However, data on performance during long-term follow-up are scarce. The aim of this study is to provide an update for the lead failure and cardiac perforation rate of Medtronic's Sprint Fidelis ICD lead (Medtronic Inc., Minneapolis, MN, USA) and St. Jude Medical's Riata ICD lead (St. Jude Medical Inc., St. Paul, MN, USA). METHODS: Since 1996, all ICD system implantations at the Leiden University Medical Center, the Netherlands, are registered. For this study, data up to February 2011 on 396 Sprint Fidelis leads (follow-up 3.4 ± 1.5 years), 165 8-French (F) Riata leads (follow-up 4.6 ± 2.6 years), and 30 7-F Riata leads (follow-up 2.9 ± 1.3 years) were compared with a benchmark cohort of 1,602 ICD leads (follow-up 3.4 ± 2.7 years) and assessed for the occurrence of lead failure and cardiac perforation. RESULTS: During follow-up, the yearly lead failure rate of the Sprint Fidelis lead, 7-F Riata lead, 8-F Riata lead, and the benchmark cohort was 3.54%, 2.28%, 0.78%, and 1.14%, respectively. In comparison to the benchmark cohort, the adjusted hazard ratio of lead failure was 3.7 (95% confidence interval [CI] 2.4-5.7, P < 0.001) for the Sprint Fidelis lead and 4.2 (95% CI 1.0-18.0, P < 0.05) for the 7-F Riata lead. One cardiac perforation was observed (3.3%) in the 7-F Riata group versus none in the 8-F Riata and Sprint Fidelis lead population. CONCLUSION: The current update demonstrates that the risk of lead failure during long-term follow-up is significantly increased for both the Sprint Fidelis and the 7-F Riata lead in comparison to the benchmark cohort. Only one cardiac perforation occurred.