Cardiac resynchronization in heart failure: Recent advances and their practical implications

Cardiac resynchronisation (CRT) improves survival and reduces heart failure hospitalisations, in symptomatic patients with heart failure (HF) with reduced ejection fraction with wide QRS despite guidelines indicated medical therapy. In patients with mild HF symptoms (New York Heart Association [NYHA], class II) CRT delays or reverses disease progression. Still, CRT is largely underused. The results of CRT Survey II indicates wide adoption of class I indications in European Society of Cardiology guidelines but with important national differences. As an example more patients in Poland had ischemic HF etiology and in NYHA III than in the overall CRT cohort. Similar patterns were seen in other countries suggesting that some patients such as those in NYHA II and with non-ischemic etiology may be especially underserved by CRT. But the Survey results also shows wide use in areas with week scientific evidence such in atrial fibrillation (AF) and when upgrading from ongoing implantable cardioverter defibrillator or right ventricular pacing to CRT. This practise may imply the belief of the physcian than CRT may but also highlights the need of randomised studies to elucidate CRT effects in such patients. Besides, gaps of evidence the review further discusses reasons for obstacles for CRT implementation and the challenges with the traditional responder definition which may deter the clinician from offering CRT therapy. Finally, the importance of sex and body size for electrical selection criteria for CRT are discussed. A person with small body size and/or female sex may may derive CRT benefit at shorter QRS durations than a bigger individual indicating the need ato shift to personalized medicine

Predictors of short-term clinical response to cardiac resynchronization therapy

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short-term clinical response. Methods and results: In an individual patient meta-analysis of three double-blind, randomized trials, clinical composite score (CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment–covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis (n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction (LVEF) as predictors of CRT clinical response (P < 0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms. Conclusions: In symptomatic chronic heart failure patients (NYHA class II–IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT

Estimation of cardiac output in patients with congestive heart failure by analysis of right ventricular pressure waveforms

<p>Abstract</p> <p>Background</p> <p>Cardiac output (CO) is an important determinant of the hemodynamic state in patients with congestive heart failure (CHF). We tested the hypothesis that CO can be estimated from the right ventricular (RV) pressure waveform in CHF patients using a pulse contour cardiac output algorithm that considers constant but patient specific RV outflow tract characteristic impedance.</p> <p>Method</p> <p>In 12 patients with CHF, breath-by-breath Fick CO and RV pressure waveforms were recorded utilizing an implantable hemodynamic monitor during a bicycle exercise protocol. These data were analyzed retrospectively to assess changes in characteristic impedance of the RV outflow tract during exercise. Four patients that were implanted with an implantable cardiac defibrillator (ICD) implementing the algorithm were studied prospectively. During a two staged sub-maximal bicycle exercise test conducted at 4 and 16 weeks of implant, COs measured by direct Fick technique and estimated by the ICD were recorded and compared.</p> <p>Results</p> <p>At rest the total pulmonary arterial resistance and the characteristic impedance were 675 ± 345 and 48 ± 18 dyn.s.cm^-5, respectively. During sub-maximal exercise, the total pulmonary arterial resistance decreased (Δ 91 ± 159 dyn.s.cm^-5, p < 0.05) but the characteristic impedance was unaffected (Δ 3 ± 9 dyn.s.cm^-5, NS). The algorithm derived cardiac output estimates correlated with Fick CO (7.6 ± 2.5 L/min, R²= 0.92) with a limit of agreement of 1.7 L/min and tracked changes in Fick CO (R²= 0.73).</p> <p>Conclusions</p> <p>The analysis of right ventricular pressure waveforms continuously recorded by an implantable hemodynamic monitor provides an estimate of CO and may prove useful in guiding treatment in patients with CHF.</p

Cost-effectiveness analysis of cardiac resynchronization therapy in patients with NYHA I and NYHA II heart failure in Spain

Objectives: The aim of the study was to combine clinical results from the European Cohort of the REVERSE study and costs associated with the addition of cardiac resynchronization therapy (CRT) to optimal medical therapy (OMT) in patients with mild symptomatic (NYHA I-II) or asymptomatic left ventricular dysfunction and markers of cardiac dyssynchrony in Spain. Methods: A Markov model was developed with CRT + OMT (CRT-ON) versus OMT only (CRT-OFF) based on a retrospective cost-effectiveness analysis. Raw data was derived from literature and expert opinion, reflecting clinical and economic consequences of patient"s management in Spain. Time horizon was 10 years. Both costs (euro 2010) and effects were discounted at 3 percent per annum. Results: CRT-ON showed higher total costs than CRT-OFF; however, CRT reduced the length of hospitalization in ICU by 94 percent (0.006 versus 0.091 days) and general ward in by 34 percent (0.705 versus 1.076 days). Surviving CRT-ON patients (88.2 percent versus 77.5 percent) remained in better functional class longer, and they achieved an improvement of 0.9 life years (LYGs) and 0.77 years quality-adjusted life years (QALYs). CRT-ON proved to be cost-effective after 6 years, except for the 7th year due to battery depletion. At 10 years, the results were 18,431 per LYG and 21,500 per QALY gained. Probabilistic sensitivity analysis showed CRT-ON was cost-effective in 75.4 percent of the cases at 10 years. Conclusions: The use of CRT added to OMT represents an efficient use of resources in patients suffering from heart failure in NYHA functional classes I and II

The burden of proof: the current state of atrial fibrillation prevention and treatment trials

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015

Upgrades from Previous Cardiac Implantable Electronic Devices Compared to De Novo Cardiac Resynchronization Therapy Implantations: Results from CRT Survey-II in the Turkish Population

Objective: Cardiac resynchronization therapy is the guideline-directed treatment option in selected heart failure with reduced left ventricular ejection fraction patients. Data regarding the contemporary clinical practice of cardiac resynchronization therapy in Turkey have been published recently. This sub-study aims to compare clinical and periprocedural characteristics between cardiac resynchronization therapy upgrade and de novo implantations. Methods: Turkish arm of the Cardiac Resynchronization Therapy Survey-II was conducted between October 1, 2015, and December 31, 2016, at 16 centers. All consecutive patients who underwent an upgrade to cardiac resynchronization therapy system (n=60) or de novo cardiac resynchronization therapy implantation (n=335) were eligible. Results: Distribution of age, gender, and heart failure etiology were similar in the 2 groups. Atrial fibrillation, valvular heart disease, and chronic kidney disease were more common in cardiac resynchronization therapy upgrade patients. Narrow intrinsic QRS duration and left ventricular ejection fraction being 75% in both groups, and only beta-blockers were prescribed at rates of >90% in both groups. Conclusion: Cardiac resynchronization therapy upgrades are performed with high procedural success rates and without excess periprocedural complication risk. Feared complications of cardiac resynchronization therapy upgrades due to the pre-existing device should not delay the procedure if indicated.publishedVersio

085: Heart failure with preserved ejection fraction: changes in clinical parameters between acute presentation and subsequent follow-up

PurposeIn the prospective KaRen registry of heart failure with preserved ejection fraction (HFPEF), changes in clinical and biological parameters and medications were assessed between acute presentation and out-patient follow-up in stable state.MethodsThe KaRen study included patients presenting with acute heart failure (HF) according to inclusion criteria: Framingham criteria for HF, left ventricular ejection fraction > or=45% and brain natriuretic peptide (BNP)>100pg/mL or NT-proBNP>300pg/mL. Once stabilized, 4-8 weeks after the index presentation, patients returned as out-patients for repeat assessment. Changes in clinical and biological parameters and medications between inclusion and follow-up were assessed with Students t-test and Chi-square testsResults577 patients were recruited and 458 returned for the 4-8 weeks visit. 56% were women. The median [25-75pctl] age was 79 [72-84] years. Medical history included 78% hypertension, 58% atrial arrhythmia, 26% type II diabetes and 27% serum creatinin >100 micromol/l. The table provides inclusion and follow-up dataConclusionsPatients presenting with HFPEF are elderly and a majority are women, with a high rate of hypertension and atrial arrhythmias. Blood pressure is incompletely controlled. At follow-up, blood pressure and NT-proBNP were reduced, but patients remain symptomatic. Still, efforts are needed to improve symptoms in HFPEF.Table (abstract 85) – Inclusion and follow-up data.Variable Mean (IQR)NYHA I / II / III / IVSBPCreatinineNT-proBNPACEI /ARBB-blockerANTICOAGInclusion0.8 / 9.4 / 40 / 49.8%148 [130-170]93 [74-128]2433 [1272-4790]60%65%41%Follow-up13 / 62.5 / 22.2 / 2.3140 [120-150]95 [75-129]1409 [514-2641]68%67.5%51.3%p<0.00010.003<0.000

Effect of QRS duration and morphology on cardiac resynchronization therapy outcomes in mild heart failure: results from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study.

International audienceBACKGROUND: Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. We aimed to assess the impact of baseline QRS duration and morphology and the change in QRS duration with pacing on CRT outcomes in mild heart failure. METHODS AND RESULTS: Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) was a multicenter randomized trial of CRT among 610 patients with mild heart failure. Baseline and CRT-paced QRS durations and baseline QRS morphology were evaluated by blinded core laboratories. The mean baseline QRS duration was 151±23 milliseconds, and 60.5% of subjects had left bundle-branch block (LBBB). Patients with LBBB experienced a 25.3-mL/m(2) mean reduction in left ventricular end-systolic volume index (P<0.0001), whereas non-LBBB patients had smaller decreases (6.7 mL/m(2); P=0.18). Baseline QRS duration was also a strong predictor of change in left ventricular end-systolic volume index with monotonic increases as QRS duration prolonged. Similarly, the clinical composite score improved with CRT for LBBB subjects (odds ratio, 0.530; P=0.0034) but not for non-LBBB subjects (odds ratio, 0.724; P=0.21). The association between clinical composite score and QRS duration was highly significant (odds ratio, 0.831 for each 10-millisecond increase in QRS duration; P<0.0001), with improved response at longer QRS durations. The change in QRS duration with CRT pacing was not an independent predictor of any outcomes after correction for baseline variables. CONCLUSION: REVERSE demonstrated that LBBB and QRS prolongation are markers of reverse remodeling and clinical benefit with CRT in mild heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271154