Cardiac resynchronization therapy in congenital heart disease: Results from the German National Register for Congenital Heart Defects.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established option for patients with heart failure. Limited data exists on indications and outcome of CRT in contemporary congenital heart disease (CHD) patients. METHODS AND RESULTS: All patients with CRT registered in the German National Register for Congenital Heart Defects were systematically identified. We analysed data on demographics, type of congenital defect as well as repair, associated conditions, indication for CRT, heart failure medication, combination with a defibrillator or pacemaker and outcome. Overall, 65 patients with CRT were identified. The most common congenital diagnoses were Tetralogy of Fallot (n = 11), congenitally corrected transposition of the great arteries (ccTGA) (n = 9) and double outlet right ventricle (n = 6). The majority of patients (n = 48, 87%) had conventional antibradycardia pacing or ICD indications. Of these, the majority (n = 44) underwent an upgrade to a CRT system to avoid the detrimental consequences of longstanding conventional ventricular single-site pacing, whereas four patients required an ICD due to heart failure and a history of malignant ventricular tachycardia. During a median follow-up of 6.9 years 19 patients developed complications: 16 patients experienced pacemaker lead dysfunction and 3 patients pacemaker infection. CONCLUSIONS: The current study based on a large national register for CHD shows that CRT is feasible and can be used as an adjunct in the heart failure treatment of selected CHD patients. Uptake of this therapy proved to be low in this nationwide study and CRT implantation was largely used in patients with a pre-existing pacing indication or those requiring an ICD.

The Hemodynamic Effects of Different Pacing Modalities After Cardiopulmonary Bypass in Patients With Reduced Left Ventricular Function.

OBJECTIVES: Patients with decreased left ventricular function undergoing cardiac surgery have a greater chance of difficult weaning from cardiopulmonary bypass and a poorer clinical outcome. Directly after weaning, interventricular dyssynchrony, paradoxical septal motion, and even temporary bundle-branch block might be observed. In this study, the authors measured arterial dP/dtmax, mean arterial pressure (MAP), and cardiac index using transpulmonary thermodilution, pulse contour analysis, and femoral artery catheter and compared the effects between right ventricular (A-RV) and biventricular (A-BiV) pacing on these parameters. DESIGN: Prospective study. SETTING: Single-center study. PARTICIPANTS: The study comprised 17 patients with a normal or prolonged QRS duration and a left ventricular ejection fraction ≤35% who underwent coronary artery bypass grafting with or without valve replacement. INTERVENTIONS: Temporary pacing wires were placed on the right atrium and both ventricles. Different pacing modalities were used in a standardized order. MEASUREMENTS AND MAIN RESULTS: A-BiV pacing compared with A-RV pacing demonstrated higher arterial dP/dtmax values (846 ± 646 mmHg/s v 800 ± 587 mmHg/s, p = 0.023) and higher MAP values (77 ± 19 mmHg v 71 ± 18 mmHg, p = 0.036). CONCLUSION: In patients with preoperative decreased left ventricular function undergoing coronary artery bypass grafting, A-BiV pacing improve the arterial dP/dtmax and MAP in patients with both normal and prolonged QRS duration compared with standard A-RV pacing. In addition, arterial dP/dtmax and MAP can be used to evaluate the effect of intraoperative pacing. In contrast to previous studies using more invasive techniques, transpulmonary thermodilution is easy to apply in the perioperative clinical setting.

Long-term management of end-stage heart failure.

End-stage heart failure manifests as severe and often relentless symptoms that define the clinical syndrome of heart failure, namely congestion and hypoperfusion. These patients suffer from dyspnea, fatigue, abdominal discomfort, and ultimately cardiac cachexia. Renal and hepatic dysfunction frequently further complicates the process. Recurrent hospitalizations, cardiac arrhythmias, and intolerance to standard heart failure therapies are common as the disease progresses. Management focuses on controlling symptoms, correcting precipitants, avoiding triggers, and maximizing therapies with demonstrable survival benefit. Among appropriate candidates, advanced therapies such as orthotopic heart transplant (OHT) can significantly extend survival and improve the quality of life. Left ventricular assist devices have been used with increasing frequency as a bridge to OHT or as a destination therapy in appropriately selected candidates where they have a demonstrable mortality benefit over medical therapy. Importantly, a multidisciplinary patient-centered approach is crucial when considering these advanced therapies.

Incremental value of cystatin C over conventional renal metrics for predicting clinical response and outcomes in cardiac resynchronization therapy: The BIOCRT study.

BACKGROUND: Despite the benefit of CRT in select patients with heart failure (HF), there remains significant need for predicting those at risk for adverse outcomes for this effective but costly therapy. CysC, an emerging marker of renal function, is predictive of worsening symptoms and mortality in patients with HF. This study assessed the utility of baseline and serial measures of cystatin C (CysC), compared to conventional creatinine-based measures of renal function (estimated glomerular filtration rate, eGFR), in predicting clinical outcomes following cardiac resynchronization therapy (CRT). METHODS: In 133 patients, we measured peripheral venous (PV) and coronary sinus (CS) CysC concentrations and peripheral creatinine levels at the time of CRT implant. Study endpoints included clinical response to CRT at 6 months and major adverse cardiac events (MACE) at 2 years. RESULTS: While all 3 renal metrics were predictive of MACE (all adjusted p ≤ 0.02), only CysC was associated with CRT non-response at 6 months (adjusted odds ratio 3.6, p = 0.02). CysC improved prediction of CRT non-response (p ≤ 0.003) in net reclassification index analysis compared to models utilizing standard renal metrics. Serial CysC > 1mg/L was associated with 6-month CRT non-response and reduced 6-minute walk distance as well as 2-year MACE (all p ≤ 0.04). CONCLUSION: In patients undergoing CRT, CysC demonstrated incremental benefit in the prediction of CRT non-response when compared to standard metrics of renal function. Baseline and serial measures of elevated CysC were predictive of CRT non-response and functional status at 6 months as well as long-term clinical outcomes.

The Role of Cardiovascular Magnetic Resonance in Cardiac Resynchronization Therapy.

Randomized, controlled trials have shown that cardiac resynchronization therapy (CRT) is beneficial in patients with heart failure, impaired left ventricular (LV) systolic function, and a wide QRS complex. Other studies have shown that targeting the LV pacing site can also improve patient outcomes. Cardiovascular magnetic resonance (CMR) is a radiation-free imaging modality that provides unparalleled spatial resolution. In addition, emerging data suggest that targeted LV lead deployment over viable myocardium improves the outcome of patients undergoing CRT. This review explores the role of CMR in the preoperative workup of patients undergoing CRT.

Circulating MicroRNA-30d Is Associated With Response to Cardiac Resynchronization Therapy in Heart Failure and Regulates Cardiomyocyte Apoptosis: A Translational Pilot Study.

BACKGROUND: Biomarkers that predict response to cardiac resynchronization therapy (CRT) in heart failure patients with dyssynchrony (HFDYS) would be clinically important. Circulating extracellular microRNAs (miRNAs) have emerged as novel biomarkers that may also play important functional roles, but their relevance as markers for CRT response has not been examined. METHODS AND RESULTS: Comprehensive miRNA polymerase chain reaction arrays were used to assess baseline levels of 766 plasma miRNAs in patients undergoing clinically indicated CRT in an initial discovery set (n=12) with and without subsequent echocardiographic improvement at 6 months after CRT. Validation of candidate miRNAs in 61 additional patients confirmed that baseline plasma miR-30d was associated with CRT response (defined as an increase in left ventricular ejection fraction ≥10%). MiR-30d was enriched in coronary sinus blood and increased in late-contracting myocardium in a canine model of HFDYS, indicating cardiac origin with maximal expression in areas of high mechanical stress. We examined the functional effects of miR-30d in cultured cardiomyocytes and determined that miR-30d is expressed in cardiomyocytes and released in vesicles in response to mechanical stress. Overexpression of miR-30d in cultured cardiomyocytes led to cardiomyocyte growth and protected against apoptosis by targeting the mitogen-associated kinase 4, a downstream effector of tumor necrosis factor. In HFDYS patients, miR-30d plasma levels inversely correlated with high-sensitivity troponin T, a marker of myocardial necrosis. CONCLUSIONS: Baseline plasma miR-30d level is associated with response to CRT in HFDYS in this translational pilot study. MiR-30d increase in cardiomyocytes correlates with areas of increased wall stress in HFDYS and is protective against deleterious tumor necrosis factor signaling.

Does prior valve surgery change outcome in patients treated with cardiac resynchronization therapy?

AIMS: Cardiac valve surgery (CVS) has been implicated as a potential barrier to optimal response after cardiac resynchronization therapy (CRT) though prospective data regarding outcome remains limited. We sought to determine CRT response in patients with a prior history of CVS. METHODS AND RESULTS: We performed a retrospective analysis of a prospectively acquired cohort of CRT patients with history of CVS. Echocardiographic response was evaluated at baseline and 6 months. The coprimary endpoints were time to first heart failure (HF) hospitalization and a composite of all-cause mortality, transplantation and left ventricular assist device (LVAD) assessed over a 3-year follow-up period. The study group consisted of 569 patients undergoing CRT. Of these, 86 patients had a history of CVS (46.5% aortic, 37.2% mitral, 16.3% combined, and tricuspid), and were compared to 483 patients with no history of CVS. Baseline clinical and echocardiographic characteristics were not significantly different between the groups except for a higher incidence of atrial fibrillation (AF; 74.4% vs. 55.3%; P = 0.001), coronary artery bypass surgery (CABG; 58.1% vs. 38.7%; P = 0.001), and longer QRS duration (167.6 ± 29.3 milliseconds vs. 159.4 ± 27.5 milliseconds; P = 0.01) in those with prior CVS. Survival with respect to HF hospitalization and composite outcome was comparable in both groups. Echocardiographic response (improvement in left ventricular ejection fraction of ≥10%) was similar. No difference in clinical or echocardiographic outcome was found by type of valve surgery performed. CONCLUSION: Despite a higher incidence of AF, CABG, and longer QRS duration, history of CVS is not associated with worse clinical or echocardiographic outcome after CRT.

Terapia de resincronización cardíaca: importancia de los cambios vasculares periféricos en la reducción de la poscarga ventricular y mejora de la eficiencia ventricular / Cardiac resyncronization therapy: importance of peripheral vascular changes en reduction of ventricular after load and improvement of ventricular efficiency

La terapia de resincronización cardíaca (TRC) asociaría cambios vasculares que contribuirían a explicar sus beneficios y a comprender las diferencias en la respuesta a la terapia. Sin embargo, actualmente la evaluación de los efectos y respuesta a la TRC se centra únicamente en la estimación de los cambios en la estructura-función ventricular. Objetivo: 1) caracterizar los cambios en la poscarga y energética ventricular izquierda asociados a la TRC, y 2) analizar la importancia de los cambios vasculares periféricos en el desempeño ventricular postTRC. Método: en 25 pacientes (14 hombres, 61±12 años) consecutivos derivados para TRC, se evaluaron parámetros estándar de estructura y función ventricular y arterial, antes y después de TRC. Se obtuvo la presión aórtica central, el gasto cardíaco (GC), la carga arterial neta, poscarga y sus determinantes. Resultado: la TRC resultó en aumento del GC y la complacencia arterial, y en reducción de la resistencia vascular periférica (RVP), impedancia aórtica, diámetros y volúmenes ventriculares (p<0,05). La conjunción de cambios ventrículo-arteriales resultó en reducción de poscarga (-19%). Si no hubiera caída de la RVP, la poscarga aumentaría (~44-56%), con reducción de la eficiencia ventricular. Conclusión: la TRC resulta en reducción de la poscarga por cambios en las diferentes componentes de carga. Los beneficios de la TRC en términos de desempeño ventricular y reducción de la poscarga se explican por cambios ventriculares y vasculares (simultáneos). La mejora ventricular con aumento del GC sin cambios vasculares periféricos asociados resultaría en detrimento de las condiciones de trabajo ventricular (aumento de poscarga)

Heart failure in 2011: Heart failure therapy--technology to the fore.

Studies published in 2011 in the field of heart failure have reinforced the benefit of cardiac resynchronization therapy in patients with mild symptoms and confirmed the value of left ventricular assist devices and CABG surgery in selected patients. Conversely, the efficacy of nesiritide in acute heart failure has been questioned.

Cardiac resynchronization therapy: current trends and future directions.

Despite the clear cut indications for cardiac resynchronization therapy (CRT) laid down by guideline forming bodies, there are numerous unresolved issues. This review article primarily focuses on the current trends in CRT and the challenges encountered in patient selection, procedure related and postimplantation patient management issues. The high rate of non-response to CRT warrants a critical appraisal of the patient selection criteria, with the role of QRS duration and use of imaging to quantify ventricular dyssynchrony being the major points of discussion. Likewise the role of CRT in relatively asymptomatic heart failure patients, those with atrial fibrillation and the benefits of providing an implantable cardioverter defibrillator backup to all CRT devices has yet to be clearly defined. The development of effective and minimally invasive surgical techniques, dependable and reproducible means for optimal pacing site localization and comparative trials on superior mode of lead positioning, pacing sites and optimized CRT programming encompassing diverse patient populations would further advance current standards of CRT. Innovative approaches to resolve these controversies and future goal directed research is needed. Development of novel, comprehensive prediction tools to identify responders to CRT and the possibility of 'leadless' pacing would be interesting futuristic prospects.