Impact of telemedical management on hospitalization and mortality in heart failure patients with diabetes: a post-hoc subgroup analysis of the TIM-HF2 trial.

BACKGROUND: The TIM-HF2 study demonstrated that remote patient management (RPM) in a well-defined heart failure (HF) population reduced the percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death during 1-year follow-up (hazard ratio 0.80) and all-cause mortality alone (HR 0.70). Higher rates of hospital admissions and mortality have been reported in HF patients with diabetes compared with HF patients without diabetes. Therefore, in a post-hoc analysis of the TIM-HF2 study, we investigated the efficacy of RPM in HF patients with diabetes. METHODS: TIM-HF2 study was a randomized, controlled, unmasked (concealed randomization), multicentre trial, performed in Germany between August 2013 and May 2018. HF-Patients in NYHA class II/III who had a HF-related hospital admission within the previous 12 months, irrespective of left ventricular ejection fraction, and were randomized to usual care with or without added RPM and followed for 1 year. The primary endpoint was days lost due to unplanned cardiovascular hospitalization or due to death of any cause. This post-hoc analysis included 707 HF patients with diabetes. RESULTS: In HF patients with diabetes, RPM reduced the percentage of days lost due to cardiovascular hospitalization or death compared with usual care (HR 0.66, 95% CI 0.48-0.90), and the rate of all-cause mortality alone (HR 0.52, 95% CI 0.32-0.85). RPM was also associated with an improvement in quality of life (mean difference in change in global score of Minnesota Living with Heart Failure Questionnaire score (MLHFQ): - 3.4, 95% CI - 6.2 to - 0.6). CONCLUSION: These results support the use of RPM in HF patients with diabetes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01878630.

Incidence of lead erosion in a real-world cohort and a case of successful treatment with an antimicrobial mesh.

Cardiac implantable electronic device (CIED)-related infections are a major complication of CIED therapy and associated with high morbidity and mortality. The aim of the present study was to evaluate the incidence of lead erosion as one cause of the CIED-related infections and to provide detailed information about the therapy of two cases of lead erosion. We retrospectively screened the database of a large clinic specialized on patients with CIED (HIZ BERLIN Herzschrittmacher- und ICD-Zentrum, Berlin, Germany) for cases of lead erosion between 2015 and 2020. A total of 5971 outpatients were treated at the HIZ BERLIN - including 4782 patients with a one- or two-chamber pacemaker, 837 patients with an implantable cardioverter defibrillator (ICD) and 352 patients with a biventricular device for cardiac resynchronization therapy (CRT). The incidence of lead erosion was 0.033%. As one of the two patients, who suffered from lead erosions, had no signs of systemic infection, the patient received local therapy with an antimicrobial mesh and intravenous antibiotics. After twelve months, he showed a good clinical outcome without ongoing or recurring infection. In conclusion, the incidence of lead erosion is low. In case of lead erosions without signs of systemic infection, an antimicrobial mesh might be implanted as an off-label use in patients that decline complete device removal.

Prevalence of left ventricular systolic dysfunction in a typical outpatient pacemaker cohort.

BACKGROUND: Right ventricular (RV) pacing is the standard treatment for symptomatic bradycardia. RV pacing is known to cause dyssyncrony. New treatment options like His bundle pacing enhance the focus on left ventricular dysfunction in patients with pacemakers. OBJECTIVES: The aim of this cross-sectional study was to obtain a real-life picture of the patients in a representative cohort of outpatients with permanent pacemakers. The prevalence and causes of left ventricular dysfunction (LVD) were explored. METHODS: In total, 1869 patients of a pacemaker outpatient clinic were screened for left ventricular systolic dysfunction by transthoracic echocardiography. All patients were interviewed for symptoms and cardiologist care. Percentages of RV pacing and underlying cardiac disease were recorded. RESULTS: A left ventricular ejection fraction (LVEF) under 45% was found in 207 (11.1%) of all patients. Predictive factors for a reduced LVEF were a high pacing rate and long-term pacing. LVD due to RV pacing was diagnosed in 3.4% of all patients. Only 845 patients (45%) reported that they regularly visited a cardiologist. CONCLUSION: There is a high prevalence of unknown LVD in a typical pacemaker cohort. Therefore, regular echocardiographic examinations should be performed in outpatients of pacemaker clinics.

Plasma Kynurenine Predicts Severity and Complications of Heart Failure and Associates with Established Biochemical and Clinical Markers of Disease.

BACKGROUND: Kynurenine, a metabolite of the L-tryptophan pathway, plays a pivotal role in neuro-inflammation, cancer immunology, and cardiovascular inflammation, and has been shown to predict cardiovascular events. OBJECTIVES: It was our objective to increase the body of data regarding the value of kynurenine as a biomarker in chronic heart failure (CHF). METHODS: We investigated the predictive value of plasma kynurenine in a CHF cohort (CHF, n = 114); in a second cohort of defibrillator carriers with CHF (AICD, n = 156), we determined clinical and biochemical determinants of the marker which was measured by enzyme immunoassay. RESULTS: In the CHF cohort, both kynurenine and NT-proBNP increased with NYHA class. Univariate binary logistic regression showed kynurenine to predict death within a 6-month follow-up (OR 1.43, 95% CI 1.03-2.00, p = 0.033) whereas NT-proBNP did not contribute significantly. Kynurenine, like NT-proBNP, was able to discriminate at a 30% threshold of left ventricular ejection fraction (LVEF; AUC-ROC, both 0.74). Kynurenine correlated inversely with LVEF (ϱ = -0.394), glomerular filtration fraction (GFR; ϱ = -0.615), and peak VO2 (ϱ = -0.626). Moreover, there was a strong correlation of kynurenine with NT-proBNP (ϱ = 0.615). In the AICD cohort, multiple linear regression analysis demonstrated highly significant associations of kynurenine with GFR, hsCRP, and tryptophan, as well as a significant impact of age. CONCLUSIONS: This work speaks in favor of kynurenine being a new and valuable biomarker of CHF, with particular attention placed on its ability to predict mortality and reflect exercise capacity.

Homoarginine Associates with Zonulin and Tryptophan - Findings in a High-Risk Cohort of Patients Carrying an AICD.

BACKGROUND: Homoarginine (hArg) is known to have an impact on nitric oxide (NO) metabolism. It seems to increase NO generation and/or availability, thereby enhancing endothelial function. In addition, hArg is connected to energy metabolism since the key enzyme, L-arginine-glycine amidinotransferase (AGAT) for hArg synthesis in the kidneys, is also involved in the synthesis of energy metabolites like guanidinoacetate. Former studies indicate that low levels of hArg are linked to cardiovascular disease and increased all-cause mortality. METHODS: This study investigated the dependence of plasma hArg on various biochemical and clinical factors in 229 patients carrying an automatic, implantable cardioverter/defibrillator (AICD) using multiple linear regression analysis (Generalized Linear Model, GLM). RESULTS: GLM revealed a highly significant, positive association between hArg and zonulin (p < 0.001). hArg was also positively correlated with tryptophan (p = 0.004), BMI (p = 0.02), and body weight (p = 0.02). Patients with hsCRP above 10 mg/L had significantly lower hArg concentrations than patients with hsCRP ≤ 10 mg/L. CONCLUSIONS: The highly significant positive association of hArg with zonulin is a novel finding which may indicate a different meaning of circulating versus local (gut) zonulin. Therefore, further experimental and clinical investigation is needed to explore this association, focusing on possible pathophysiological pathways and the role of circulating zonulin levels in cardiovascular disease. The positive correlation of hArg and Trp also deserves further research because both amino acids might have a protective effect on cardiovascular disease by inhibition of the enzyme alkaline phosphatase. Eventually, our study associates low hArg concentrations with chronic low-grade inflammation and parameters of malnutrition in cardiovascular high-risk patients.

Surgery for prosthetic valve endocarditis: associations between morbidity, mortality and costs.

OBJECTIVES: Surgery for prosthetic valve endocarditis (PVE) is associated with significant morbidity and mortality as well as with increased resource utilization and costs. For risk and cost reduction, an understanding of contributing factors and interrelations is essential. METHODS: Out of 1080 heart valve procedures performed between January 2010 and December 2012, 41 patients underwent surgery for PVE. Complete economic data were available for 30 of them (study cohort). The patients' mean age was 64 ± 12 years (range 37-79 years), and 73% were men. The clinical course was reviewed and morbidity, mortality and costs as well as associations between them were analysed. The cost matrix for each individual patient was obtained from the Institute for the Hospital Remuneration System (InEK GmbH, Germany). The median follow-up was 2.6 years [interquartile range (IQR) 3.7 years; 100% complete]. RESULTS: Preoperative status was critical (EuroSCORE II >20%) in 43% of patients. Staphylococci were the most common infecting micro-organisms (27%). The operative mortality rate (≤30 days) was 17%. At 1 year, the overall survival rate was 71 ± 9%. At least one disease- or surgery-related complication affected 21 patients (early morbidity 70%), >1 complication affected 12 patients (40%). There was neither a recurrence of endocarditis, nor was a reoperation required. The mean total hospital costs were 42.6 ± 37.4 Thousand Euro (T€), median 25.7 T€, IQR 28.4 T€ and >100 T€ in 10% of cases. Intensive care unit/intermediate care (ICU/IMC) and operation accounted for 40.4 ± 18.6 and 25.7 ± 12.1% of costs, respectively. There was a significant correlation (Pearson's sample correlation coefficient) between total costs and duration of hospital stay (r = 0.83, P < 0.001) and between ICU/IMC costs and duration of ICU/IMC stay (r = 0.97, P < 0.001). The median daily hospital costs were 1.8 T€/day, but >2.4 T€/day in 25% of patients (upper quartile). The following pattern of associations was identified (P < 0.05). Early mortality was related to preoperative morbidity and postoperative renal failure. Early morbidity was associated with preoperative morbidity and urgency. Total costs were mainly explained by preoperative morbidity, postoperative morbidity and urgency. High EuroSCORE II, complex surgery, need for mechanical circulatory support as well as postoperative mortality and morbidity increased daily costs. CONCLUSIONS: The timely diagnosis and treatment of these patients must be a priority, as preoperative morbidity is the major contributor towards mortality, morbidity and costs after surgery for PVE.

Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation.

BACKGROUND: The tight junction regulator zonulin has attracted clinical attention as a biomarker of increased gastrointestinal permeability. Recent work also suggests zonulin to represent a general regulator of tissue barriers and a player in metabolic inflammation. Here, we investigated the associations of zonulin with chronic heart failure (CHF), kidney function, and metabolic inflammation. METHODS: Using multiple linear regression (Generalized Linear Model), this study determined the association of plasma zonulin with different laboratory and clinical parameters in 225 patients carrying automatic implantable cardioverters/defibrillators (AICD) for primary or secondary prevention. In another 115 patients with diastolic or systolic CHF, we investigated a possible relationship between zonulin and CHF severity. RESULTS: In the AICD cohort, zonulin associated inversely with serum creatinine (p = 0.013), carboxymethyl-lysine calprotectin (p < 0.001), and kynurenine (p = 0.009) and positively with homoarginine (p < 0.001). In the subgroup with type-2 diabetes (T2D) (n = 51), zonulin increased significantly with high-sensitivity CRP (p = 0.014). In the CHF cohort, we found a highly significant rise of NT-proBNP, but not of zonulin with NYHA functional classes I-IV or other parameters of CHF severity. CONCLUSIONS: The inverse associations of zonulin with creatinine and markers of cardio-vascular risk (high CMLcalprotectin and kynurenine, low homoarginine) are novel findings that need further experimental and clinical clarification. Our study indicates zonulin involvement in metabolic inflammation in T2D, but no association with disease status in CHF.

Efficacy of optimal medical therapy and cardiac resynchronization therapy upgrade in patients with pacemaker-induced cardiomyopathy.

PURPOSE: The aim of our study was to assess the prevalence of pacemaker-induced cardiomyopathy (PMiCMP) and its response to biventricular stimulation and optimal medical therapy. METHODS: To identify patients with PMiCMP, we screened all patients that presented for pacemaker interrogation in our outpatient clinic in 2012 and 2013 (n = 615). Left ventricular (LV) function was assessed by transthoracic echocardiography. PMiCMP was defined as deterioration of left ventricular ejection fraction (LVEF) <45% unexplained by other cardiac disease under a right ventricular (RV) pacing percentage ≥90%. If symptoms and LV dysfunction persisted under heart failure medication, patients were offered to receive an upgrade to biventricular stimulation (cardiac resynchronization therapy, CRT). CRT response was defined as a decrease of the LV end-systolic volume (LVESV) of ≥15%. RESULTS: Thirty-seven patients were found to have a PMiCMP. The prevalence of PMiCMP in our total cohort was 6.0%. In 20 PMiCMP patients, an upgrade to a CRT device was performed after a minimum of 3 months of optimal medical therapy. The remaining PMiCMP patients either refused an upgrade or were in good functional status. The LVEF before CRT upgrade was 33.3 ± 5.2% and improved to 47.6 ± 9.3% (P < 0.001) within 6 months. Positive response to CRT was observed in 17 patients (85%). In the group without device upgrade, LVEF was 40.5 ± 5% and did not change during the follow-up period of 1 year. CONCLUSIONS: Optimal medical therapy lacks efficacy in PMiCMP patients. The response rate to CRT was significantly higher in PMiCMP patients compared to average CRT patients.

Prevalence of E/A wave fusion and A wave truncation in DDD pacemaker patients with complete AV block under nominal AV intervals.

AIMS: Optimization of the AV-interval (AVI) in DDD pacemakers improves cardiac hemodynamics and reduces pacemaker syndromes. Manual optimization is typically not performed in clinical routine. In the present study we analyze the prevalence of E/A wave fusion and A wave truncation under resting conditions in 160 patients with complete AV block (AVB) under the pre-programmed AVI. We manually optimized sub-optimal AVI. METHODS: We analyzed 160 pacemaker patients with complete AVB, both in sinus rhythm (AV-sense; n = 129) and under atrial pacing (AV-pace; n = 31). Using Doppler analyses of the transmitral inflow we classified the nominal AVI as: a) normal, b) too long (E/A wave fusion) or c) too short (A wave truncation). In patients with a sub-optimal AVI, we performed manual optimization according to the recommendations of the American Society of Echocardiography. RESULTS: All AVB patients with atrial pacing exhibited a normal transmitral inflow under the nominal AV-pace intervals (100%). In contrast, 25 AVB patients in sinus rhythm showed E/A wave fusion under the pre-programmed AV-sense intervals (19.4%; 95% confidence interval (CI): 12.6-26.2%). A wave truncations were not observed in any patient. All patients with a complete E/A wave fusion achieved a normal transmitral inflow after AV-sense interval reduction (mean optimized AVI: 79.4 ± 13.6 ms). CONCLUSIONS: Given the rate of 19.4% (CI 12.6-26.2%) of patients with a too long nominal AV-sense interval, automatic algorithms may prove useful in improving cardiac hemodynamics, especially in the subgroup of atrially triggered pacemaker patients with AV node diseases.

Clinical, anatomical, and technical risk factors for postoperative pacemaker or defibrillator lead perforation with particular focus on myocardial thickness.

BACKGROUND: Postoperative lead perforation is a life-threatening complication of cardiac pacing. Identification of precipitating factors for this serious complication may help to anticipate a specific risk profile and to minimize the incidence. METHODS: We conducted a retrospective tertiary referral center analysis to clarify clinical, anatomical, and technical characteristics related to pacemaker (PM) and cardioverter/defibrillator lead perforation. We examined the baseline characteristics and the symptoms. In a subgroup, we investigated the myocardial thickness on contrast-enhanced cardiac computed tomography. RESULTS: We enrolled 26 patients. Female gender appears to put patients at slightly increased risk for lead perforation. In a majority active fixation leads were used. Symptoms occurred in 72%. Pericardial effusion and tamponade were present in 38% and 19%, respectively. Sensing was compromised in 65%. A high pacing threshold or exit block occurred in 92%. Myocardial thickness did not differ between patients with or without perforation. In 96%, the perforation was treated by transvenous withdrawal. CONCLUSION: Chest pain, phrenic stimulation, bad sensing, or exit block early after PM implantation must prompt radiological and echocardiographic evaluation. A missing pericardial effusion particularly late after implantation does not rule out a perforation. Especially active fixating leads have a higher risk of perforation. With cardiac surgery in standby transvenous withdrawal is a safe way to treat lead perforation.

Outcome after surgery for prosthetic valve endocarditis and the impact of preoperative treatment.

OBJECTIVES: This study examined the outcomes of surgery for active prosthetic valve endocarditis in a recent decade, with special interest in preoperative treatment and predictors for early and late events. METHODS: From 2000 to 2010, a cohort of 149 consecutive patients (mean age, 64±13.9 years; 72% were male) underwent redo-surgery for prosthetic valve endocarditis and were reviewed regarding early (≤60 days) and late (>60 days) events (death, reinfection, reoperation). Kaplan-Meier survival curves and Cox regression analysis were used to investigate the impact of preoperative intervals and predictors for events, respectively. RESULTS: Preoperative status was critical (European System for Cardiac Operative Risk Evaluation>20%) in 121 patients (81.2%). Staphylococci were the most common infecting microorganisms (27.5%). The median interval between onset of symptoms and diagnosis and between diagnosis and operation was 2 days (interquartile range, 1-5) and 8 days (interquartile range, 2-23), respectively. Operative mortality (≤30 days) was 12.8%. Mean follow-up was 4±2.9 years. In 53 patients, 47 early (24 deaths, 14 recurrences, 9 reoperations) and 22 late events (11 deaths, 9 recurrences, 2 reoperations) occurred. Overall and event-free survivals at 10 years were 75%±3.8% and 64%±4.0%, respectively. Freedom from recurrent infection and reoperation at 10 years were 81%±3.6% and 91%±2.6%, respectively. In multivariate Cox regression, mechanical circulatory support, prolongation between onset of symptoms and diagnosis more than 30 days, and preoperative presence of renal failure predicted early events, and double valve replacement predicted late events. CONCLUSIONS: Cardiac and renal function, need for double valve replacement, and preoperative treatment predicted outcomes. A prolonged interval in which patients were left untreated while symptomatic, but not prolongation of preoperative antibiotic treatment, increased risk.

Not left ventricular lead position, but the extent of immediate asynchrony reduction predicts long-term response to cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an effective treatment for a large subgroup of chronic heart failure patients. Various attempts to improve the high non-responder rate of 30 % by preoperative asynchrony assessment have failed. We hypothesized that superior response to CRT is correlated with greater acute reduction of asynchrony and that a concordant left ventricular (LV) lead is beneficial compared to a discordant lead. Hundred and eight consecutive CRT patients from our center were prospectively included. Clinical status and asynchrony parameters were assessed before, 1 day and 6 months after CRT implantation. Super-response was defined as an increase of the LV ejection fraction by ≥15 % and a decrease in LV end systolic volume (LVESV) by ≥30 %. When the criteria for super-response were not met, average response was given with a decrease of baseline LVESV ≥15 %. Sixty eight patients were classified as responders (63 %). Comparing super- (n = 19) and average (n = 49) responders, we found that greater acute reduction of LV asynchrony (change of asynchronous segments under CRT: -1.3 vs. -0.4, p < 0.05; decrease of LV intraventricular delay: -34 ms vs. -16 ms, p < 0.05) is associated with superior reverse remodeling after 6 months. Importantly, asynchrony parameters of super-, average and non-responders were almost identical at baseline. A concordant LV lead (n = 63) was not associated with improved LV reverse remodeling compared to a discordant lead (n = 28): LVEF: +8.6 % vs. +7.8 %, p = 0.91; LVESV: -30.5 ml vs. -23.8 mL, p = 0.84. A greater immediate reduction of LV asynchrony predicts superior response. Preoperative asynchrony parameters do not correlate with outcome. A concordant LV lead is not superior to a discordant lead.

Complete atrioventricular block after TAVI: when is pacemaker implantation safe?

INTRODUCTION: Atrioventricular (AV) block is a frequent complication of transcatheter aortic valve implantation (TAVI). TAVI is routinely performed under anticoagulation using heparin, which potentially may lead to an increased bleeding rate in patients who undergo permanent pacemaker (PPM) implantation immediately after TAVI. As the number of TAVI procedures continues to rise, data on the optimal management of TAVI-related AV block are needed. Therefore, the aim of our study was to analyze PPM implantation-related complications after TAVI. METHODS: We retrospectively collected data on PPM implantations after TAVI in our center from January 2010 to December 2012. In total, we included 30 patients who received a PPM for TAVI-related AV block. Twelve patients (group A) underwent PPM implantation on the day of TAVI. In 18 patients (group B), PPM implantation was performed at least 1 day after TAVI (3.8 ± 4.5 days). Since all patients undergoing TAVI receive dual antiplatelet therapy (DA-therapy), we compared all implantations after TAVI with a historic patient cohort that underwent PPM implantation under DA-therapy. RESULTS: Procedure times, fluid loss via drainage systems, and drainage times were neither significantly different between groups A and B nor between all PPM implantations after TAVI compared to the historic control group. CONCLUSION: PPM implantation immediately after TAVI is safe and can be performed without increased rate of complications.

Left ventricular asynchrony in patients with right bundle branch block and normal ejection fraction.

AIMS: The role of right bundle branch block (RBBB) for the induction of left ventricular (LV) asynchrony is discussed controversially. The objective of this study was to assess presence and degree of LV asynchrony in patients with RBBB, left bundle branch block (LBBB), or left anterior hemiblock (LAH) and normal LV function. METHODS: We included 15 patients with RBBB, 13 patients with RBBB and concomitant LAH, 10 patients with pure LBBB, and 100 healthy controls into this study. All patients had normal LV function. Interventricular asynchrony was assessed as the difference of the right and LV ejection delay. Intraventricular delay was obtained by tissue synchronicity imaging-guided tissue Doppler imaging measurement. RESULTS: Interventricular and left intraventricular asynchrony were linked to the presence of an LBBB. No left intraventricular asynchrony was noted during pure RBBB; interventricular delays were negative (aortic flow preceding pulmonary flow) in the presence of RBBB. CONCLUSION: In patients with normal LV function, intraventricular asynchrony depends on the presence of an LBBB and interventricular asynchrony is inversed in the presence of RBBB.

Therapy of cardiac device pocket infections with vacuum-assisted wound closure-long-term follow-up.

BACKGROUND: Cardiac device infections are serious complications that require aggressive treatment strategies, including interventional or surgical lead extraction. METHODS: Here we describe the long-time follow-up of vacuum-assisted closure (V.A.C.) treatment in five patients with local cardiac device infection (LDI). In these patients the device was removed, the electrodes were shortened, and a V.A.C. treatment was applied. The primary endpoint was defined as time to re-LDI. RESULTS: Three patients had LDI of a pacemaker pocket, whereas two presented with an infection of their ICD pocket. The V.A.C. treatment was applied for 34.4 ± 17.9 days. The mean hospitalization time was 38.6 ± 19.2 days. The follow-up period was assessed for 34.6 ± 19.2 months. Only one patient developed re-LDI, 69 days after removal of the device. The other four patients did not show any signs of reinfection during the follow-up period. None of the five patients sustained serious adverse events. CONCLUSIONS: V.A.C. treatment may be an option for selected patients with LDI who refuse a laser-guided lead extraction or surgical removal of the electrodes as the primary therapy.

Pacing-induced cardiomyopathy in patients with right ventricular stimulation for >15 years.

AIMS: The prevalence of pacing-induced cardiomyopathy (PiCMP) has been reported to be 9% 1 year after implantation. As long-term data are sparse, the aim of our study was to evaluate the prevalence of PiCMP in a cohort of patients with at least 15 years of right ventricular (RV) pacing. METHODS AND RESULTS: Inclusion criteria were RV stimulation for at least 15 years due to atrioventricular block III° and absence of structural heart disease at the time of initial implantation. All patients were examined by echocardiography and spiroergometry. Pacing-induced cardiomyopathy was pre-defined as left ventricular (LV) ejection fraction (LVEF) ≤45%, dyskinesia during RV pacing and absence of other known causes of cardiomyopathy. Twenty-six patients from our outpatient department met the inclusion criteria. Pacing-induced cardiomyopathy was diagnosed in four patients (15.4%). Echocardiography showed significant LV remodelling in PiCMP patients [LVEF 41.0 ± 4.5%, LV end-diastolic diameter (LVEDD) 54.0 ± 2.7 mm] compared with patients with preserved LVEF (LVEF 61.2 ± 5.8%, P = 0.002, LVEDD 45.6 ± 4.0 mm, P= 0.004). There were no significant differences regarding age, gender, duration of RV pacing, heart rate, interventricular mechanical delay, QRS duration or prevalence of sinus rhythm, and arterial hypertension between both groups. The longest intraventricular delay was significantly shorter in patients with preserved LVEF (65.5 ± 43.0 ms) compared with PiCMP patients (112.5 ± 15.0 ms, P= 0.043). Exercise capacity and quality of life did not differ significantly between both groups. CONCLUSION: Considering the very long duration of RV stimulation in our study population (24.6 ± 6.6 years), the prevalence of PiCMP was remarkably low. Pacing-induced cardiomyopathy was associated with more pronounced intraventricular dyssynchrony.

Dyssynchrony parameter-guided interventricular delay programming.

AIMS: Interventricular (VV) delay optimization for cardiac resynchronization therapy (CRT) is recommended by current guidelines and several algorithms have been proposed. So far, however, no gold standard has been established in the clinical routine. We hypothesized that dyssynchrony parameter assessment might guide VV delay optimization and investigated whether dyssynchrony parameter changes induced by sequential biventricular pacing follow a predictable pattern. METHODS AND RESULTS: We determined intra- and interventricular dyssynchrony in 80 CRT patients by echocardiographic quantification of the interventricular mechanical delay and the septal-lateral time to peak systolic velocity delay. Dyssynchrony parameters were assessed during simultaneous biventricular pacing as well as during sequential biventricular pacing with a right ventricular (RV) or left ventricular (LV) preactivation of 40 ms. Simultaneous biventricular pacing significantly improved inter- and intraventricular dyssynchrony parameters compared with preoperative baseline measurements. In general, dyssynchrony parameter changes induced by sequential biventricular pacing showed high interindividual variance and did not follow a predictable pattern. Intra- or interventricular dyssynchrony persisted during simultaneous biventricular pacing in 39 and 19% of our patients, respectively. Neither RV nor LV preactivation significantly decreased the number of patients with persistent intraventricular dyssynchrony. In contrast, LV preactivation significantly reduced the prevalence of interventricular dyssynchrony by 80%. CONCLUSIONS: Left ventricular preactivation effectively ameliorates interventricular dyssynchrony, which persists in almost one in five CRT patients. Assessment of interventricular dyssynchrony and consecutive programming of LV preactivation in patients with persistent interventricular dyssynchrony may represent a pragmatic and time-effective approach to improve CRT in patients with inferior response.

Successful reduction of intraventricular asynchrony is associated with superior response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is generally associated with a low to moderate increase of the left ventricular ejection fraction (LVEF). In some patients, however, LVEF improves remarkably and reaches near-normal values. The aim of the present study was to further characterize these so called 'super-responders' with a special focus on the extent of intra- and interventricular asynchrony before and after device implantation compared to average responders. METHODS: 37 consecutive patients who underwent CRT device implantation according to current guidelines were included in the study. Patients were examined by echocardiography before, one day after and six months after device implantation. Pre-defined criterion for superior response to CRT was an LVEF increase > 15% after six months. RESULTS: At follow-up, eight patients (21.6%) were identified as super-responders. There were no significant differences regarding age, gender, prevalence of ischemic heart disease and LVEF between average and super-responders at baseline. After six months, LVEF had significantly increased from 26.7% ± 5.7% to 33.1% ± 7.9% (p < 0.001) in average and from 24.0% ± 6.7% to 50.3% ± 7.4% (p < 0.001) in super-responders. Both groups showed a significant reduction of QRS duration as well as LV end-diastolic and -systolic volumes under CRT. At baseline, the interventricular mechanical delay (IVMD) was 53.7 ± 20.9 ms in average and 56.9 ± 22.4 ms in super-responders - representing a similar extent of interventricular asynchrony in both groups (p = 0.713). CRT significantly reduced the IVMD to 20.3 ± 15.7 (p < 0.001) in average and to 19.8 ± 15.9 ms (p = 0.013) in super-responders with no difference between both groups (p = 0.858). As a marker for intraventricular asynchrony, we assessed the longest intraventricular delay between six basal LV segments. At baseline, there was no difference between average (86.2 ± 30.5 ms) and super-responders (78.8 ± 23.6 ms, p = 0.528). CRT significantly reduced the longest intraventricular delay in both groups--with a significant difference between average (66.2 ± 36.2 ms) and super-responders (32.5 ± 18.3 ms, p = 0.022). Multivariate logistic regression analysis identified the longest intraventricular delay one day after device implantation as an independent predictor of superior response to CRT (p = 0.038). CONCLUSIONS: A significant reduction of the longest intraventricular delay correlates with superior response to CRT.