Targeted left ventricular lead positioning to the site of latest activation in cardiac resynchronization therapy: a systematic review and meta-analysis.

AIMS: Several studies have evaluated the use of electrically- or imaging-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT) recipients. We aimed to assess evidence for a guided strategy that targets LV lead position to the site of latest LV activation. METHODS AND RESULTS: A systematic review and meta-analysis was performed for randomized controlled trials (RCTs) until March 2023 that evaluated electrically- or imaging-guided LV lead positioning on clinical and echocardiographic outcomes. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization, and secondary endpoints were quality of life, 6-min walk test (6MWT), QRS duration, LV end-systolic volume, and LV ejection fraction. We included eight RCTs that comprised 1323 patients. Six RCTs compared guided strategy (n = 638) to routine (n = 468), and two RCTs compared different guiding strategies head-to-head: electrically- (n = 111) vs. imaging-guided (n = 106). Compared to routine, a guided strategy did not significantly reduce the risk of the primary endpoint after 12-24 (RR 0.83, 95% CI 0.52-1.33) months. A guided strategy was associated with slight improvement in 6MWT distance after 6 months of follow-up of absolute 18 (95% CI 6-30) m between groups, but not in remaining secondary endpoints. None of the secondary endpoints differed between the guided strategies. CONCLUSION: In this study, a CRT implantation strategy that targets the latest LV activation did not improve survival or reduce heart failure hospitalizations.

Impact of His bundle pacing on right ventricular performance in patients undergoing permanent pacemaker implantation.

BACKGROUND: His-Bundle pacing (HBP) is an emerging technique for physiological pacing. However, its effects on right ventricle (RV) performance are still unknown. METHODS: We enrolled consecutive patients with an indication for pacemaker (PM) implantation to compare HBP versus RV pacing (RVP) effects on RV performance. Patients were evaluated before implantation and after 6 months by a transthoracic echocardiogram. RESULTS: A total of 84 patients (age 75.1±7.9 years, 64% male) were enrolled, 42 patients (50%) underwent successful HBP, and 42 patients (50%) apical RVP. At follow up, we found a significant improvement in RV-FAC (Fractional Area Change)% [baseline: HBP 34 IQR (31-37) vs. RVP 33 IQR (29.7-37.2),p = .602; 6-months: HBP 37 IQR (33-39) vs. RVP 30 IQR (27.7-35), p < .0001] and RV-GLS (Global Longitudinal Strain)% [baseline: HBP -18 IQR (-20.2 to -15) vs. RVP -16 IQR (-18.7 to -14), p = .150; 6-months: HBP -20 IQR(-23 to -17) vs. RVP -13.5 IQR (-16 to -11), p < .0001] with HBP whereas RVP was associated with a significant decline in both parameters. RVP was also associated with a significant worsening of tricuspid annular plane systolic excursion (TAPSE) (p < .0001) and S wave velocity (p < .0001) at follow up. Conversely from RVP, HBP significantly improved pulmonary artery systolic pressure (PASP) [baseline: HBP 38 IQR (32-42) mmHg vs. RVP 34 IQR (31.5-37) mmHg,p = .060; 6-months: HBP 32 IQR (26-38) mmHg vs. RVP 39 IQR (36-41) mmHg, p < .0001] and tricuspid regurgitation (p = .005) irrespectively from lead position above or below the tricuspid valve. CONCLUSIONS: In patients undergoing PM implantation, HBP ensues a beneficial and protective impact on RV performance compared with RVP.

Clinical and Humoral Determinants of Congestion in Heart Failure: Potential Role of Adiponectin.

BACKGROUND: Some patients with heart failure (HF) are more prone to systemic congestion than others. The goal of this study was to identify clinical and humoral factors linked to congestion and its prognostic impact in HF patients. METHODS: A total of 371 advanced HF patients underwent physical examination, echocardiography, right heart catheterization, blood samplings, and Minnesota Living with HF Questionnaire. Subjects were followed-up for adverse events (death, urgent transplantation, or assist device implantation without heart transplantation). RESULTS: Thirty-one percent of patients were classified as prone to congestion. During a median follow-up of 1,093 days, 159 (43%) patients had an adverse event. In the Cox analysis, the congestion-prone (CP) status was associated with a 43% higher event risk. The CP status was strongly (p ˂ 0.001) associated with body weight loss, right ventricular dysfunction (RVD), dilated inferior vena cava (IVC), diuretics, and beta-blockers prescription and the majority of tested hormones in the univariate analysis. In the multivariate analysis, the only independent variables associated with the CP status were adiponectin, albumin, IVC diameter, and RVD. Adiponectin by itself was predictive of adverse events. In a multivariate model, CP status was no longer predictive of adverse events, in contrast to adiponectin. CONCLUSIONS: CP patients experienced more severe symptoms and had shorter survival. Potential role of adiponectin, a new independent predictor of CP status, should be further examined.

The effect of ICD programming on inappropriate and appropriate ICD Therapies in ischemic and nonischemic cardiomyopathy: the MADIT-RIT trial.

INTRODUCTION: The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy. METHODS AND RESULTS: First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with nonischemic cardiomyopathy. Patients with ischemic and nonischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy (HR range 0.11-0.34, P < 0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and nonischemic cardiomyopathy patients. CONCLUSION: High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy.

Clinical impact and predictors of periprocedural myocardial injury among patients undergoing left bundle branch area pacing.

BACKGROUND: The clinical impact of Periprocedural myocardial injury (PMI) in patients undergoing permanent pacemaker implantation with Left Bundle Branch Area Pacing (LBBAP) is unknown. METHODS: 130 patients undergoing LBBAP from January 2020 to June 2021 and completing 12 months follow up were enrolled to assess the impact of PMI on composite clinical outcome (CCO) defined as any of the following: all-cause death, hospitalization for heart failure (HHF), hospitalization for acute coronary syndrome (ACS) and ventricular arrhythmias (VAs). High sensitivity Troponin T (HsTnT) was measured up to 24-h after intervention to identify the peak HsTnT values. PMI was defined as increased peak HsTnT values at least > 99th percentile of the upper reference limit (URL: 15 pg/ml) in patients with normal baseline values. RESULTS: PMI occurred in 72 of 130 patients (55%). ROC analysis yielded a post-procedural peak HsTnT cutoff of fourfold the URL for predicting the CCO (AUC: 0.692; p = 0.023; sensitivity 73% and specificity 71%). Of the enrolled patients, 20% (n = 26) had peak HsTnT > fourfold the URL. Patients with peak HsTnT > fourfold the URL exhibited a higher incidence of the CCO than patients with peak HsTnT ≤ fourfold the URL (31% vs. 10%; p = 0.005), driven by more frequent hospitalizations for ACS (15% vs. 3%; p = 0.010). Multiple (> 2) lead repositions attempts, the use of septography and stylet-driven leads were independent predictors of higher risk of PMI with peak HsTnT > fourfold the URL. CONCLUSIONS: PMI seems common among patients undergoing LBBAP and may be associated with an increased risk of clinical outcomes in case of more pronounced (peak HsTnT > fourfold the URL) myocardial damage occurring during the procedure.

A case report of upgrading to cardiac resynchronization therapy in a patient with congenitally corrected transposition of great arteries and dextrocardia.

Background: Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital heart anomaly. Physiological correction may be associated with a long pre-symptomatic period in many patients and delayed accidental diagnosis. Additional related congenital malformations may increase the complexity of cardiac interventions. Case summary: A 59-year-old man with known dextrocardia, situs viscerum inversus, and CCTGA was scheduled for upgrading of a dual-chamber pacemaker to cardiac resynchronization therapy to treat heart failure related to a progressive systolic dysfunction of the systemic right ventricle (RV). Because of the specific anatomy of this patient, the therapeutic procedure was complicated by the cannulation of the Marshall vein. Nevertheless, the left ventricular lead was successfully implanted into the coronary sinus lateral branch. At the 3-month follow-up, the patient remarkably reported a significant functional improvement, despite no favourable reverse remodelling of the systemic RV. Discussion: Upgrade of a pacemaker to biventricular pacing was feasible in this patient, who had CCTGA and dextrocardia, which resulted in symptomatic improvement at follow-up. Pre-implant contrast cardiac computed tomography angiography was essential for visualizing the venous-specific anatomy in this patient, who suffered from congenital heart disease. Conduction system pacing represents a potential alternative for the patient to prevent or treat pacing-related heart failure.

Feasibility and safety of left bundle branch area pacing-cardiac resynchronization therapy in elderly patients.

BACKGROUND: Left bundle branch area pacing (LBBAP) is an emerging technique to achieve cardiac resynchronization therapy (CRT), but its feasibility and safety in elderly patients with heart failure with reduced ejection fraction and left bundle branch block is hardly investigated. METHODS: We enrolled consecutive patients with an indication for CRT comparing pacing parameters and complication rates of LBBAP-CRT in elderly patients (≥ 75 years) versus younger patients (< 75 years) over a 6-month follow-up. RESULTS: LBBAP was successful in 55/60 enrolled patients (92%), among which 25(45%) were elderly. In both groups, LBBAP significantly reduced the QRS duration (elderly group: 168 ± 15 ms to 136 ± 12 ms, p < 0.0001; younger group: 166 ± 14 ms to 134 ± 11 ms, p < 0.0001) and improved LVEF (elderly group: 28 ± 5% to 40 ± 7%, p < 0.0001; younger group: 29 ± 5% to 41 ± 8%, p < 0.0001). The pacing threshold was 0.9 ± 0.8 V in the elderly group vs. 0.7 ± 0.5 V in the younger group (p = 0.350). The R wave was 9.5 ± 3.9 mV in elderly patients vs. 10.7 ± 2.7 mV in younger patients (p = 0.341). The fluoroscopic (elderly: 13 ± 7 min vs. younger: 11 ± 7 min, p = 0.153) and procedural time (elderly: 80 ± 20 min vs. younger: 78 ± 16 min, p = 0.749) were comparable between groups. Lead dislodgement occurred in 2(4%) patients, 1 in each group (p = 1.000). Intraprocedural septal perforation occurred in three patients (5%), 2(8%) in the elderly group (p = 0.585). One patient (2%) in the elderly group had a pocket infection. CONCLUSIONS: LBBAP is a feasible and safe technique for delivering physiological pacing in elderly patients who are candidates for CRT with suitable pacing parameters and low complication rates.

Small left atrium and mild mitral regurgitation predict super-response to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) can result in profound reverse remodelling. The goal of this study was to identify factors predictive of such beneficial response. METHODS AND RESULTS: Super-response to CRT was defined as normalization or near normalization of left ventricular systolic function without recognized reversible causes of heart failure. In a retrospective study, we compared baseline demographic, electrocardiogram, and echocardiographic characteristics of super-responders (n = 21) with a population of unselected consecutive cardiac CRT patients (Control 1, n = 330) and another sex-, age-, and aetiology-matched control group (Control 2, n = 43). Compared with Control 1, super-responders had significantly smaller left ventricular end-diastolic diameter (65.4 ± 6.4 vs. 73.4 ± 9.3 mm, P = 0.0001), higher ejection fraction (0.25 ± 0.05 vs. 0.22 ± 0.04, P = 0.004), smaller degree of mitral regurgitation (MR; mean value 1.9 ± 0.9 vs. 2.6 ± 0.8, P = <0.0001), and smaller left atrium (LA; 42.8 ± 4.6 vs. 50.0 ± 6.5 mm, P < 0.0001). Septal flash and inter-ventricular mechanical dyssynchrony were both more frequent among super-responders than in Control 2 subjects (93.8 vs. 69.8%; P = 0.01, and 93.8 vs. 62.8%; P = 0.01, respectively). In a multivariate analysis, smaller LA diameter and milder MR remained independent predictors of super-response. CONCLUSION: Super-response to cardiac CRT was associated with less advanced left-sided structural involvement as described by echocardiography. In particular, smaller LA and milder MR were independent predictors of pronounced reverse remodelling.

Inadvertent QRS prolongation by an optimization device-based algorithm in patients with cardiac resynchronization therapy.

BACKGROUND: Device-based algorithms offer the potential for automated optimization of cardiac resynchronization therapy (CRT), but the process for accepting them into clinical use is currently still ad-hoc, rather than based on pre-clinical and clinical testing of specific features of validity. We investigated how the QuickOpt-guided VV delay (VVD) programming performs against the clinical and engineering heuristic of QRS complex shortening by CRT. METHODS: A prospective, 2-center study enrolled 37 consecutive patients with CRT. QRS complex duration (QRSd) was assessed during intrinsic atrioventricular conduction, synchronous biventricular pacing, and biventricular pacing with QuickOpt-proposed VVD. The measurements were done manually by electronic calipers in signal-averaged and magnified 12-lead QRS complexes. RESULTS: Native QRSd was 174 ± 22 ms. Biventricular pacing with empiric AVD and synchronous VVD resulted in QRSd 156 ± 20 ms, a significant narrowing from the baseline QRSd by 17 ± 27 ms, P = 0.0003. In 36 of 37 patients, the QuickOpt algorithm recommended left ventricular preexcitation with VVD of 42 ± 18 ms (median 40 ms; interquartile range 30-55 ms, P <0.00001). QRSd in biventricular pacing with QuickOpt-based VVD was significantly longer compared with synchronous biventricular pacing (168 ± 25 ms vs. 156 ± 20 ms; difference 12 ± 11ms; P <0.00001). This prolongation correlated with the absolute VVD value (R = 0.66, P <0.00001). CONCLUSIONS: QuickOpt algorithm systematically favours a left-preexcitation VVD which translates into a significant prolongation of the QRSd compared to synchronous biventricular pacing. There is no reason to believe that a manipulation that systematically widens QRSd should be considered to optimize physiology. Device-based CRT optimization algorithms should undergo systematic mechanistic pre-clinical evaluation in various scenarios before they are tested in large clinical studies.

ILEEM-survey on the Heart Team approach and team training for lead extraction procedures.

BACKGROUND: The Heart Team approach has become an integral part of modern cardiovascular medicine. To evaluate current opinions and real-world practice among lead extraction practitioners, an online survey was created and distributed among a pool of lead extraction specialists participating in the International Lead Extraction Expert Meeting (ILEEM) 2018. METHODS: The online survey consisted of 10 questions and was performed using an online survey tool (www.surveymonkey.com). The collector link was sent to 48 lead extraction experts via email. RESULTS: A total of 43 answers were collected (89% return rate) from lead extraction experts in 16 different countries. A great majority (83.7%) of the respondents performed more than 30 lead extraction procedures per year. The most common procedural environment in this survey was the hybrid operating room (67.4%). Most procedures were performed by electrophysiologists and cardiologists (80.9%). Important additional members of the current lead extraction teams were cardiac surgeons (79.1%), anesthesiologists (95.3%) and operating room scrub nurses (76.7%). An extended Heart Team is regarded beneficial for patient care by 86.0%, with potential further members being infectious diseases specialists, intensivists and radiologists. Team training activities are performed in 48.8% of participating centers. CONCLUSIONS: This survey supports the importance of establishing lead extraction Heart Teams in specialized lead extraction centers to potentially improve patient outcomes. The concept of a core and an extended Heart Team approach in lead extraction procedures is introduced.

Impact of cardiac resynchronization therapy on the severity of mitral regurgitation.

AIMS: Functional mitral regurgitation (MR) could be managed by both cardiac resynchronization therapy (CRT) and mitral-valve surgery. Clinical decision making regarding the appropriateness of mitral-valve surgery vs. CRT is a challenging task. This study assessed the prevalence and prognosis of various degrees of functional MR in CRT candidates. Additionally, we sought to identify functional MR patients who either can be adequately managed by CRT only or will need surgery. METHODS AND RESULTS: Cardiac resynchronization therapy recipients (n= 794) were followed-up for 26 ± 18 months. Mitral regurgitation severity was quantified on scale 0-4. Cardiac resynchronization therapy responders were identified based on improvement in the New York Heart Association class and left-ventricular ejection fraction. Severity of MR and LV reverse remodelling were assessed at 3 and 12 months. Predictors of long-term MR change and CRT response were explored with multivariable models. Mitral regurgitation was present in 86%, with 35% prevalence of advanced MR (grade 3-4). Improvement of MR ≥ 1° after 12 months occurred in 46% of patients. It was relatively more frequent in patients with advanced MR at baseline (63%, P< 0.01). Baseline MR severity and change in MR at 3-month follow-up predicted response to CRT. Patients with ≥ 1° MR improvement at 12 months had more reverse remodelling compared with those with no change or worsening of MR. CONCLUSIONS: Mitral regurgitation improvement at 3 months predicts CRT response and MR improvement at 12-month follow-up. This finding could have implications for subsequent MR surgical therapies.

Long-Term Outcome of Patients With Congenital Heart Disease Undergoing Cardiac Resynchronization Therapy.

Background Cardiac resynchronization therapy (CRT) is rarely used in patients with congenital heart disease, and reported follow-up is short. We sought to evaluate long-term impact of CRT in a single-center cohort of patients with congenital heart disease. Methods and Results Thirty-two consecutive patients with structural congenital heart disease (N=30) or congenital atrioventricular block (N=2), aged median of 12.9 years at CRT with pacing capability device implantation, were followed up for a median of 8.7 years. CRT response was defined as an increase in systemic ventricular ejection fraction or fractional area of change by >10 units and improved or unchanged New York Heart Association class. Freedom from cardiovascular death, heart failure hospitalization, or new transplant listing was 92.6% and 83.2% at 5 and 10 years, respectively. Freedom from CRT complications, leading to surgical system revision (elective generator replacement excluded) or therapy termination, was 82.7% and 72.2% at 5 and 10 years, respectively. The overall probability of an uneventful therapy continuation was 76.3% and 58.8% at 5 and 10 years, respectively. There was a significant increase in ejection fraction/fractional area of change (P<0.001) mainly attributable to patients with systemic left ventricle (P=0.002) and decrease in systemic ventricular end-diastolic dimensions (P<0.05) after CRT. New York Heart Association functional class improved from a median 2.0 to 1.25 (P<0.001). Long-term CRT response was present in 54.8% of patients at last follow-up and was more frequent in systemic left ventricle (P<0.001). Conclusions CRT in patients with congenital heart disease was associated with acceptable survival and long-term response in ≈50% of patients. Probability of an uneventful CRT continuation was modest.

Simple electrophysiological predictor of QRS change induced by cardiac resynchronization therapy: A novel marker of complete left bundle branch block.

BACKGROUND: QRS complex shortening by cardiac resynchronization therapy (CRT) has been associated with improved outcomes. OBJECTIVE: We hypothesized that the absence of QRS duration (QRSd) prolongation by right ventricular mid-septal pacing (RVP) may indicate complete left bundle branch block (cLBBB). METHODS: We prospectively collected 12-lead surface electrocardiograms (ECGs) and intracardiac electrograms during CRT implant procedures. Digital recordings were edited and manually measured. The outcome measure was a change in QRSd induced by CRT (delta CRT). Several outcome predictors were investigated: native QRSd, cLBBB (by using Strauss criteria), interval between the onset of the QRS complex and the local left ventricular electrogram (Q-LV), and a newly proposed index defined by the difference between RVP and native QRSd (delta RVP). RESULTS: One hundred thirty-three consecutive patients were included in the study. Delta RVP was 27 ± 25 ms, and delta CRT was -14 ± 28 ms. Delta CRT correlated with native QRSd (r = -0.65), with the presence of ECG-based cLBBB (r = -0.40), with Q-LV (r = -0.68), and with delta RVP (r = 0.72) (P < .00001 for all correlations). In multivariable analysis, delta CRT was most strongly associated with delta RVP (P < .00001), followed by native QRSd and Q-LV, while ECG-based cLBBB became a nonsignificant factor. CONCLUSION: Baseline QRSd, delta RVP, and LV electrical lead position (Q-LV) represent strong independent predictors of ECG response to CRT. The absence of QRSd prolongation by RVP may serve as an alternative and more specific marker of cLBBB. Delta RVP correlates strongly with the CRT effect on QRSd and outperforms the predictive value of ECG-based cLBBB.

Myocardial ketone body utilization in patients with heart failure: The impact of oral ketone ester.

AIMS: Upregulation of ketone body (ß-hydroxybutyrate, ßHB) utilization has been documented in human end-stage heart failure (HF), but is unclear if this is due to intrinsic cardiac metabolic remodeling or a HF-related catabolic state. This study sought to evaluate the maximal ketone body utilization capacity and its determinants in controls and in patients with moderate HF and reduced ejection fraction (HFrEF). METHODS AND RESULTS: 19 HFrEF patients and 9 controls underwent sampling from the arterial circulation (A) and coronary sinus (CS) to measure transmyocardial extraction of energy-providing substrates and oxygen. In a separate experiment, measurements were performed 80-min after oral administration of 25 g of ketone ester (KE, (R)-3-hydroxybutyl(R)-3-hydroxybutyrate) drink in 11 HFrEF and 6 control subjects. There were no statistically significant differences in fasting substrate levels and fractional extractions between HF and controls. Administration of KE increased ßHB by 12.9-fold, revealing an increased ability to utilize ketones in HFrEF as compared to controls (fractional extraction, FE%: 52 vs 39%, p = 0.035). ßHB FE% correlated directly with ßHB myocardial delivery (r = 0.90), LV mass (r = 0.56), LV diameter (r = 0.65) and inversely with LV EF (-0.59) (all p < 0.05). ßHB FE% positively correlated with lactate FE% (p < 0.01), but not with FFA or glucose FE%, arguing against substrate competition. CONCLUSIONS: Acute nutritional ketosis enhances ßHB extraction in patients with HFrEF compared to controls, and this enhancement correlates with degree of cardiac dysfunction and remodeling. Data suggest that subclinical metabolic remodeling occurs early in HF progression. Further studies are needed to determine whether exogenous ketones may have a potential therapeutic role.

Isolated left ventricular pacing results in worse long-term clinical outcome when compared with biventricular pacing: a single-centre randomized study.

AIMS: The objective of this study was to compare long-term clinical effects of biventricular pacing with isolated left ventricular pacing. METHODS AND RESULTS: Forty consecutive patients with idiopathic dilated cardiomyopathy and indication for cardiac resynchronization therapy were randomized to biventricular or isolated left ventricular pacing. Clinical and echocardiographic parameters were studied regularly prior to implantation and during 1 year of follow-up. Patients with atrial fibrillation were excluded from the study. A retrospective cross-sectional outcome analysis was performed 4 years after the beginning of the study. Biventricular pacing was associated with more pronounced clinical and echocardiographic benefit compared with left ventricular pacing. Biventricular pacing was associated with significantly more distinct reverse remodelling. Left ventricular ejection fraction improved by 12.5 per cent-points (95% CI 7.3-17.7) compared with 5.1 per cent-points (95% CI 1.1-9.2) (P = 0.01) and left ventricular end-diastolic diameter decreased by 8.69 mm (95% CI 5.2-12.2) compared with 5.1 mm (95% CI 1.5-8.7) (P = 0.05) in the biventricular and left-ventricular pacing group, respectively. Semi-quantitative summarization of response points revealed a greater benefit in the biventricular vs. left ventricular pacing group [mean sum of response points 3.25 (95% CI 2.62-3.88) vs. 2.35 (95% CI 1.74-2.96), respectively, P = 0.06]. After 3 years of follow-up, there was no cardiovascular death in the biventricular pacing group compared with three cardiovascular deaths in the left ventricular pacing group. CONCLUSION: In patients with idiopathic dilated cardiomyopathy, biventricular pacing is associated with significantly more pronounced benefit in clinical outcomes and reverse remodelling. A retrospective analysis after 3 years of follow-up suggests that isolated left ventricular pacing may be associated with a higher mortality rate compared with biventricular pacing.

Association between PPARalpha gene polymorphisms and myocardial infarction.

PPARalpha (peroxisome-proliferator-activated receptor alpha) regulates the expression of genes that are involved in lipid metabolism, tissue homoeostasis and inflammation. Consistent rodent and human studies suggest a link between PPARalpha function and cardiovascular disease, qualifying PPARalpha [PPARA in HUGO (Human Genome Organisation) gene nomenclature] as a candidate gene for coronary artery disease. In the present study, we comprehensively evaluated common genetic variations within the PPARalpha gene and assessed their association with myocardial infarction. First, we characterized the linkage disequilibrium within the PPARalpha gene in an initial case-control sample of 806 individuals from the Regensburg Myocardial Infarction Family Study using a panel of densely spaced SNPs (single nucleotide polymorphisms) across the gene. Single SNP analysis showed significant association with the disease phenotype [OR (odds ratio)=0.74, P=0.012, 95% CI (confidence interval)=0.61-0.94 for rs135551]. Moreover, we identified a protective three-marker haplotype with an association trend for myocardial infarction (OR=0.76, P=0.067, 95% CI=0.56-1.02). Subsequently, we were able to confirm the single SNP and haplotype association results in an independent second case-control cohort with 667 cases from the Regensburg Myocardial Infarction Family Study and 862 control individuals from the WHO (World Health Organization) MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg project (OR=0.87, P=0.046, 95% CI=0.72-0.99 for rs135551 and OR=0.80, P=0.034, 95% CI=0.65-0.98 for the three-marker haplotype respectively). From these cross-sectional association results, we provide evidence that common variations in the PPARalpha gene may influence the risk of myocardial infarction in a European population.

Common polymorphisms in the cannabinoid CB2 receptor gene (CNR2) are not associated with myocardial infarction and cardiovascular risk factors.

Myocardial infarction (MI) is a complex disease. Multiple genes and their interaction with various environmental factors influence the pathogenesis of MI that is thought to be tightly regulated by inflammatory pathways. Recent progress in genetic analysis includes the use of large-scale genome-wide association studies that have proven to be powerful tools even in the analysis of multifactorial phenotypes. However, certain genes are only sparsely represented on the available gene chips and additional candidate gene approaches are necessary. One such example is the CNR2 gene, encoding the cannabinoid receptor 2 (CB2), which has been implicated in mediating anti-inflammatory and anti-atherosclerotic effects in vivo. We therefore hypothesized that genetic variations within the CNR2 gene are associated with the development of MI or classic cardiovascular risk factors. In a large case-control study, 1,968 individuals from the German MI family study were examined with 13 single nucleotide polymorphisms (SNPs) covering CNR2 and the adjacent genes. The association of these SNPs with MI or cardiovascular risk factors, such as arterial hypertension, obesity, hypercholesterolemia and diabetes mellitus, was determined. In allelic and genotypic models, none of the SNPs showed a significant association with MI. Separate analyses for men and women revealed no gender-specific relationship between common genetic variations within the CNR2 gene and MI. Moreover, no significant association between CNR2 gene variants and common cardiovascular risk factors was observed. We therefore provide evidence in a large German population that common polymorphisms within the CNR2 gene confer no susceptibility to MI or to cardiovascular risk factors.

Lymphotoxin-alpha and galectin-2 SNPs are not associated with myocardial infarction in two different German populations.

Recent data provided strong evidence for the association of single nucleotide polymorphisms (SNPs) in the lymphotoxin-alpha (LTA) and galectin-2 (LGALS2) genes with myocardial infarction (MI) in a Japanese population. For populations of other genetic background, the relevance of these polymorphisms in the pathogenesis of MI remains controversial. We aimed to define the role of LTA and LGALS2 SNPs in two German MI populations with markedly different ascertainment strategies. Two different MI populations were studied. In the first population, MI patients were ascertained by a strong family history of MI (n = 1214). Controls were unrelated disease-free participants of the study (n = 1080). The second population included patients suffering from sporadic (nonfamilial) MI from the German KORA register (n = 607). The control group consisted of participants of the WHO MONICA survey in Germany (n = 1492). TaqMan assays were used to determine the genotypes of 4 SNPs in the LTA genomic region and 1 SNP in the LGALS2 gene. Single SNPs in both genomic regions as well as haplotypes in the LTA genomic region were tested for association in various models of inheritance. No association with MI could be found for any of the examined SNPs in the LTA genomic region and LGALS2 gene, or for haplotypes spanning the LTA genomic region. In two MI populations of European descent with markedly different ascertainment strategies, we were not able to identify a significant association of SNPs in the LTA genomic region or the LGALS2 gene with MI. These variants are unlikely to play a significant role in populations of European origin.

Cardiac resynchronization therapy guided by cardiac magnetic resonance imaging: A prospective, single-centre randomized study (CMR-CRT).

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms of heart failure (HF), morbidity and mortality in selected population. The aim of the study was to investigate the impact of cardiac magnetic resonance (CMR)-guided left ventricular (LV) lead placement on clinical outcomes and LV reverse remodelling in CRT recipients. METHODS: Patients with CRT indication were randomized for CMR-guided (CMR group) or electrophysiologically guided (EP group) LV lead placement between 2011 and 2014. The target site in the CMR group was defined as the most delayed, scar-free, in the EP group as the site with the longest interval between the QRS onset and local electrogram. The primary endpoint was a combination of cardiovascular death or HF hospitalization. Secondary endpoints were New York Heart Association (NYHA) Class improvement ≥1, LV endsystolic diameter reduction >10%, B-type natriuretic peptide reduction by ≥30%. RESULTS: A total of 99 patients (47 in the CMR and 52 in the EP group) were enrolled. During a median follow-up of 47 months, primary composite endpoint occurred in 5 patients in the CMR group and 14 patients in the EP group (HR = 0.46; 95% CI: 0.16-1.32). Patients with left bundle branch block and NYHA Class >2 had better clinical outcome in the CMR group (HR = 0.09; 95% CI: 0.01-0.75). CONCLUSIONS: The use of CMR did not result in significant reduction of combined endpoint of cardiovascular death or HF hospitalization in the total study population. Significant clinical benefit from CMR-guided procedure was observed in a subgroup of optimum CRT candidates with advanced HF.