Timing of Complete Multivessel Revascularization in Patients Presenting With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Complete revascularization of the culprit and all significant nonculprit lesions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD) reduces major adverse cardiac events, but optimal timing of revascularization remains unclear. OBJECTIVES: This study aims to compare immediate complete revascularization (ICR) and staged complete revascularization (SCR) in patients presenting with NSTE-ACS and MVD. METHODS: This prespecified substudy of the BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease) trial included patients with NSTE-ACS and MVD. Risk differences of the primary composite outcome of all-cause mortality, myocardial infarction (MI), unplanned ischemia-driven revascularization (UIDR), or cerebrovascular events and its individual components were compared between ICR and SCR at 1 year. RESULTS: The BIOVASC trial enrolled 1,525 patients; 917 patients presented with NSTE-ACS, of whom 459 were allocated to ICR and 458 to SCR. Incidences of the primary composite outcome were similar in the 2 groups (7.9% vs 10.1%; risk difference 2.2%; 95% CI: -1.5 to 6.0; P = 0.15). ICR was associated with a significant reduction of MIs (2.0% vs 5.3%; risk difference 3.3%; 95% CI: 0.9 to 5.7; P = 0.006), which was maintained after exclusion of procedure-related MIs occurring during the index or staged procedure (2.0% vs 4.4%; risk difference 2.4%; 95% CI: 0.1 to 4.7; P = 0.032). UIDRs were also reduced in the ICR group (4.2% vs 7.8%; risk difference 3.5%; 95% CI: 0.4 to 6.6; P = 0.018). CONCLUSIONS: ICR is safe in patients with NSTE-ACS and MVD and was associated with a reduction in MIs and UIDRs at 1 year.

Impact of recurrent ischaemic and bleeding events on quality of life in patients with acute coronary syndrome: Insights from the FORCE-ACS registry.

OBJECTIVE: Patients with acute coronary syndrome (ACS) remain at high risk for recurrent ischaemic and bleeding events during follow-up. Our study aimed to quantify and compare the impact of these adverse events on quality of life (QoL). METHODS: Data from patients with ACS prospectively enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for this study. The primary ischaemic and bleeding events of interest were hospital readmission for ACS and Bleeding Academic Research Consortium type 2 or 3 bleeding during 12 months follow-up. QoL was measured using the EQ-5D Visual Analogue Scale (VAS) score and the 12-item Short Form Survey version 2 derived Physical Component Summary (PCS) and Mental Health Component Summary (MCS) scores at 12 months follow-up. RESULTS: In total, 3339 patients (mean age 66.8 years, 27.9% women) were included. During follow-up, ischaemic events occurred in 202 patients (6.0%) and bleeding events in 565 patients (16.9%). After adjustment for demographic and clinical characteristics, ischaemic events remained independently associated with lower QoL regardless of metric used. Bleeding was also independently associated with lower EQ-5D VAS and PCS scores, but not with a lower MCS score. The QoL decrement associated with ischaemic events was numerically larger than the decrement associated with bleeding. CONCLUSIONS: Ischaemic and bleeding events remain prevalent and are independently associated with lower QoL at 12 months follow-up in patients previously admitted for ACS. The incidence and impact of these adverse events should be considered when balancing individual ischaemic and bleeding risks.

External validation of the GRACE risk score and the risk-treatment paradox in patients with acute coronary syndrome.

OBJECTIVES: To validate the Global Registry of Acute Coronary Events (GRACE) risk score and examine the extent and impact of the risk-treatment paradox in contemporary patients with acute coronary syndrome (ACS). METHODS: Data from 5015 patients with ACS enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for model validation. The performance of the GRACE risk score for predicting in-hospital and 1-year mortality was evaluated based on indices of model discrimination and calibration. Differences in the delivery of guideline-recommended care among patients who survived hospitalisation (n=4911) per GRACE risk stratum were assessed and the association with postdischarge mortality was examined. RESULTS: Discriminative power of the GRACE risk score was good for predicting in-hospital (c-statistic: 0.86; 95% CI: 0.83 to 0.90) and 1-year mortality (c-statistic: 0.82; 95% CI: 0.79 to 0.84). However, the GRACE risk score overestimated the absolute in-hospital and 1-year mortality risk (Hosmer-Lemeshow goodness-of-fit test p<0.01). Intermediate-risk and high-risk patients were 12% and 29% less likely to receive optimal guideline-recommended care compared with low-risk patients, respectively. Optimal guideline-recommended care was associated with lower mortality in intermediate- and high-risk patients. CONCLUSIONS: The GRACE risk score identified patients at higher risk for in-hospital and 1-year mortality, but overestimated absolute risk levels in contemporary patients. Optimal guideline-recommended care was associated with lower mortality in intermediate-risk and high-risk patients, but was less likely to be delivered with increasing mortality risk.

Impact of Poststenting Fractional Flow Reserve on Long-Term Clinical Outcomes: The FFR-SEARCH Study.

[Figure: see text].

Rationale and Design of the Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome (FORCE-ACS) Registry: Towards "Personalized Medicine" in Daily Clinical Practice.

Diagnostic and treatment strategies for acute coronary syndrome have improved dramatically over the past few decades, but mortality and recurrent myocardial infarction rates remain high. An aging population with increasing co-morbidities heralds new clinical challenges. Therefore, in order to evaluate and improve current treatment strategies, detailed information on clinical presentation, treatment and follow-up in real-world patients is needed. The Future Optimal Research and Care Evaluation in patients with Acute Coronary Syndrome (FORCE-ACS) registry (ClinicalTrials.gov Identifier: NCT03823547) is a multi-center, prospective real-world registry of patients admitted with (suspected) acute coronary syndrome. Both non-interventional and interventional cardiac centers in different regions of the Netherlands are currently participating. Patients are treated according to local protocols, enabling the evaluation of different diagnostic and treatment strategies used in daily practice. Data collection is performed using electronic medical records and quality-of-life questionnaires, which are sent 1, 12, 24 and 36 months after initial admission. Major end points are all-cause mortality, myocardial infarction, stent thrombosis, stroke, revascularization and all bleeding requiring medical attention. Invasive therapy, antithrombotic therapy including patient-tailored strategies, such as the use of risk scores, pharmacogenetic guided antiplatelet therapy and patient reported outcome measures are monitored. The FORCE-ACS registry provides insight into numerous aspects of the (quality of) care for acute coronary syndrome patients.

Percutaneous complete revascularization strategies using sirolimus-eluting biodegradable polymer-coated stents in patients presenting with acute coronary syndrome and multivessel disease: Rationale and design of the BIOVASC trial.

BACKGROUND: Complete revascularization in patients with an acute coronary syndrome and multivessel disease is superior compared to culprit-only treatment. However, it is unknown whether direct complete or staged complete revascularization should be pursued. METHODS: The BIOVASC study is an investigator-initiated, prospective, multicenter, randomized, 2-arm, international, open-label, noninferiority trial. We will randomize 1,525 patients 1:1 to immediate complete revascularization (experimental arm) or culprit-only plus staged complete revascularization (control arm). Patients will be enrolled in approximately 30 sites in Belgium, Italy, the Netherlands, and Spain. The primary end point is a composite of all-cause mortality, nonfatal myocardial infarction, any unplanned ischemia-driven revascularization (excluding staged procedures in the control arm at the predetermined time), and cerebrovascular events (MACCE) at 1 year post index procedure. CONCLUSIONS: The BIOVASC study aims to further refine the treatment algorithm for acute coronary syndrome patients with multivessel disease in terms of optimal timing for complete revascularization (Clinicaltrials.gov NCT03621501).

Long-term outcome in patients treated with first- versus second-generation drug-eluting stents for the treatment of unprotected left main coronary artery stenosis.

OBJECTIVE AND BACKGROUND: The study aim is to provide long-term clinical outcome after percutaneous coronary intervention (PCI) for unprotected left main coronary arteries (ULMCA) stenosis with the first-generation (1st -gen) drug-eluting stents (DES) in comparison to 2nd -gen DES, since this is largely unknown. METHODS: Between May 2002, and December 2014, a consecutive series of 656 all-comer patients underwent a PCI for ULMCA stenosis at the Erasmus Medical Center. A total of 235 patients were treated with 1st -gen DES, while a total of 421 patients were treated with 2nd -gen DES. RESULTS: Overall, the population consisted of 73% males and 58% presented with an acute coronary syndrome. Median follow-up time was 1,361 days (range from 0 to 5,031). At 5 years, the cumulative incidence of major adverse clinical events (the primary composite endpoint of all-cause death, any myocardial infarction or target lesion revascularization; MACE) did not differ between 1st - and 2nd -gen DES (36.8 vs. 38.6%, respectively, Log Rank p = .79, adjusted hazard ratio [HR] = 1.28 [95% confidence interval (CI) 0.94-1.74]). No difference was found in the individual endpoints of all-cause mortality (29.5 vs. 29% respectively, p = .88, adjusted HR = 1.19 [95% CI, 0.84-1.68]), target vessel myocardial infarction (5.0 vs. 8.4%, p = 0.17, adjusted HR = 1.75 [95% CI, 0.78-3.96]) and target lesion revascularization (8.1 vs. 9.8%, p = .94, adjusted HR = 1.16 [95% CI, 0.59-2.29]) between the 1st - and 2nd -gen DES cohorts, respectively. CONCLUSIONS: In this large cohort of consecutive patients treated for ULMCA stenosis, no significant differences were found in the safety and efficacy of 1st versus 2nd -gen DES at 5 years follow-up.

Routine Fractional Flow Reserve Measurement After Percutaneous Coronary Intervention.

BACKGROUND: Fractional flow reserve (FFR) is the current gold standard to determine hemodynamic severity of angiographically intermediate coronary lesions. Much less is known about the prognostic effects of FFR measured directly after percutaneous coronary intervention (PCI). The aims of this study were to evaluate post-PCI FFR values, identify predictors for a low post-PCI FFR, and to investigate whether a relationship between postprocedural FFR and outcome during 30-day follow-up exists. METHODS AND RESULTS: The FFR-SEARCH (Fractional Flow Reserve-Stent Evaluated at Rotterdam Cardiology Hospital) is a prospective registry in which FFR measurements were performed after PCI in 1000 consecutive patients. All FFR measurements were performed under maximum hyperemia with intravenous adenosine with the Navvus RXi system (ACIST Medical Systems, Eden Prairie, MN). The clinical end point was defined as a composite of death, target vessel revascularization, or nonfatal myocardial infarction at 30-day follow-up. Measurement of post-PCI FFR was successful in 959 patients (96%), and a total of 1165 lesions were assessed. There were no complications related to the microcatheter. A total of 322 ST-segment-elevation myocardial infarction patients with 371 measured lesions were excluded leaving 637 patients with 794 measured lesions for the final analysis. Overall post-PCI FFR was 0.90±0.07. In 396 lesions (50%), post-PCI FFR was >0.90. A total of 357 patients (56%) had ≥1 lesion(s) with a post-PCI FFR ≤0.90, and 73 patients (11%) had ≥1 lesion(s) with a post-PCI FFR ≤0.80 with post-PCI FFR ≤0.80 in 78 lesions (9.8%). Complex lesion characteristics, use of multiple stents and smaller reference vessel diameter was associated with post-PCI FFR ≤0.90. During follow-up, 11 patients (1.8%) reached the clinical end point. There was no significant relationship between post-PCI FFR and the clinical end point at 30-day follow-up ( P=0.636). CONCLUSIONS: Routine measurement of post-PCI FFR using a monorail microcatheter is safe and feasible. Several lesion and patient characteristics were associated with a low post-PCI FFR. Post-PCI FFR did not correlate with clinical events at 30 days.

Occurrence and predictors of acute stent recoil-A comparison between the xience prime cobalt chromium stent and the promus premier platinum chromium stent.

OBJECTIVES: To compare the occurrence of acute stent recoil in two different stent types (platinum chromium and cobalt chromium) and identify the potential predictors of significant acute stent recoil. BACKGROUND: Acute stent recoil is frequently observed after percutaneous coronary intervention and has been associated with in-stent restenosis and in-stent thrombosis. Different stent designs may result in varying degrees of stent recoil. METHODS: From a registry of "all-comers" treated with either the Xience Prime Cobalt Chromium or Promus Premier Platinum Chromium stent, a random sample of 100 patients was drawn. Acute stent recoil was defined as the minimal luminal diameter (MLD) of the last inflated balloon minus the MLD after, divided by the MLD of the last inflated balloon. Significant acute stent recoil was defined as recoil ≥10%. RESULTS: A total of 123 lesions (61 Xience Prime vs 62 Promus Premier) in 100 patients were analyzed. Acute stent recoil of 8.6 ± 4.9% was observed in the Xience Prime group versus 8.7 ± 4.2% in the Promus Premier group, P = 0.970. In a multivariate model for significant acute stent recoil, a stent/vessel ratio ≥1 (hazard ratio 4.64 [1.94-11.12], P = 0.001), a balloon/stent ratio >1 (hazard ratio 3.83 [1.12-13.14], P = 0.032) and direct stenting (hazard ratio 0.42 [0.18-0.96], P = 0.039) were identified as predictors. CONCLUSIONS: No significant differences were observed in the extent of acute stent recoil between the Xience Prime and the Promus Premier stent. A larger stent/vessel ratio, a larger balloon/stent ratio, and direct stenting were associated with significant acute stent recoil ≥10%. © 2017 Wiley Periodicals, Inc.

Clinical Characteristics and Management of Coronary Artery Perforations: A Single-Center 11-Year Experience and Practical Overview.

BACKGROUND: Coronary artery perforation (CAP) is a potentially lethal complication of percutaneous coronary intervention. We report on the incidence, clinical characteristics, and management of iatrogenic coronary perforations based on an 11-year single-center experience. METHODS AND RESULTS: From February 9, 2005, through November 20, 2016, 150 CAP cases were identified from our percutaneous coronary intervention database of 21 212 procedures (0.71%). Mean age of CAP patients was 66±11 years, and 62.7% were male. Treated lesion type was B2/C in 94.6%, and 31.3% were chronic total occlusions. Nonworkhorse guidewires were applied in 74.3%. CAP types were Ellis type I in 2.9%, Ellis type II in 40.4%, Ellis type III in 54.8%, and Ellis type III cavity spilling in 1.9%. CAP treatment was conservative (including prolonged balloon inflation) in 73.3%. Covered stents, coiling, and fat embolization were used in 24.0%, 0.7%, and 2.0%, respectively. Pericardiocentesis for tamponade was required for 72 patients (48.0%), of whom 28 were initially unrecognized. Twelve patients (12.7%) required emergency cardiac surgery to alleviate tamponade. Periprocedural myocardial infarction occurred in 34.0%, and in-hospital all-cause mortality was 8.0%. All-cause mortality accrued to 10.7% at 30 days and 17.8% at 1 year. CONCLUSIONS: CAP is a rare complication of percutaneous coronary intervention, but morbidity and mortality are considerable. Early recognition and adequate management are of paramount importance.

The Promus Premier everolimus-eluting platinum chromium stent with durable polymer evaluated in a real world all-comer population in Rotterdam cardiology hospital (the P-SEARCH registry).

BACKGROUND: A new-generation everolimus eluting platinum-chromium stent (EePCS), offering improved radial strength, radiopacity and conformability compared to everolimus-eluting cobalt-chromium stents (EeCCS), was evaluated with regard to safety and efficacy in an all-comer cohort. METHODS: A total of 1000 consecutive all-comer patients (including acute coronary syndrome, multivessel disease, calcified lesions) treated with an EePCS (Promus Premier™, Boston Scientific, Natick, Massachusetts) from May 2013 to October 2014 were compared to 1000 consecutive patients treated with an EeCCS (Xience Prime™, Abbott Vascular, Santa Clara, California) from April 2012 to May 2013. Patients were clinically followed for 1year. RESULTS: Mean age was 66±12years with diabetes in 20.7%, previous infarction in 22.7%, and ACS as the indication in 71.2% of patients. The mean number of stents per patient was 1.8±1.13. Total stented length was 35±25mm. Lesion classification was B2/C in 73.9% of patients. At 1year the primary endpoint of major adverse cardiac events (all-cause mortality, myocardial infarction [MI], ischemia-driven target vessel revascularization [TVR]) was reached in 11.7% in the EePCS cohort and 10.9% in the EeCCS cohort (adjusted HR 1.01 [0.77-1.33]; p=0.95). No significant differences were noted in the individual clinical endpoints all-cause mortality (6.8% versus 6.4%), MI (2.2% versus 2.3%), and TVR (4.3% versus 3.7%) in the respective EePCS and EeCCS cohorts. Stent thrombosis occurred in 0.8% and 1.0% respectively. CONCLUSIONS: In all-comer patients undergoing percutaneous coronary intervention, the use of EePCS was associated with similar 1-year clinical outcome as compared to EeCCS.

QRS fusion complex analysis using wave interference to predict reverse remodeling during cardiac resynchronization therapy.

BACKGROUND: Biventricular (BV) electrical wavefront fusion can induce improvement in left ventricular (LV) size and function during cardiac resynchronization therapy (CRT). Changes in BV wave propagation sequence and duration register in the QRS complex on the standard electrocardiogram. We developed a wave interference method for the characterization of BV fusion to predict LV reverse remodeling. OBJECTIVE: To develop a simple electrocardiographic method for predicting reverse remodeling during CRT. METHODS: QRS complexes during left bundle branch block (LBBB) and CRT were analyzed in 375 patients with ejection fraction ≤35% and New York Heart Association class III-IV (Leiden study: n = 226) as well as in patients with ejection fraction ≤40% and New York Heart Association class I-II (REVERSE trial: n = 149) for predictors of ≥10% reduction in left ventricular end-systolic volume at 6 months. CRT-induced changes in ventricular activation (QRS fusion contour), electrical asynchrony (QRS difference = BV-paced QRS - LBBB QRS, in milliseconds), and LBBB substrate (LV activation time and QRS score for LV scar) were quantified. RESULTS: Multivariable predictors of reverse remodeling were as follows: (1) either of 2 BV fusion patterns: QRS normalization in leads V1 and V2 (n = 66 [18%]; odds ratio [OR] 3.71; 95% confidence interval [CI] 1.26-10.94) or a new or an increased R wave in leads V1-V2 (n = 267 [71%]; OR 1.55; 95% CI 0.65-3.65); (2) QRS difference ≤ -25 ms (OR 2.35; 95% CI 1.12-4.91); and (3) good substrate (low to moderate QRS score and LV activation time ≥110 ms; OR 2.94; 95% CI 1.68-5.14). Remodeling rates were 40% for poor substrate and persistent LBBB QRS complex (absent BV fusion; QRS type 3: n = 42 [11%]) and 97% for the best BV QRS fusion pattern and greater reduction in electrical asynchrony (larger QRS difference). CONCLUSION: Easily determined QRS complex attributes before and after CRT predict LV reverse remodeling.

Impact of clinical and echocardiographic response to cardiac resynchronization therapy on long-term survival.

BACKGROUND: Clinical or echocardiographic mid-term responses to cardiac resynchronization therapy (CRT) may have a different influence on a long-term prognosis of heart failure patients treated with CRT. The aim of the evaluation was to establish which definition of response to CRT, clinical or echocardiographic, best predicts long-term prognosis. METHODS AND RESULTS: A total of 679 heart failure patients treated with CRT were included. All the patients underwent a complete history and physical examination and transthoracic echocardiogram prior to CRT implantation and at 6-month follow-up. The clinical and echocardiographic responses to CRT were defined based on clinical improvement (≥1 NYHA class) and LV reverse remodelling (reduction in LV end-systolic volume ≥15%) at 6-month follow-up, respectively. All the patients were prospectively followed up for the occurrence of death. The mean age was 65 ± 11 years and 79% of the patients were male. At 6-month follow-up, 510 (77%) patients showed clinical response to CRT and 412 (62%) patients showed echocardiographic response to CRT. During a mean follow-up of 37 ± 22 months, 140 (21%) patients died. Clinical and echocardiographic responses to CRT were both significantly related to all-cause mortality on univariable analysis. However, on multivariable Cox-regression analysis only echocardiographic response to CRT was independently associated with superior survival (hazard ratio: 0.38; 95% CI: 0.27-0.50; P < 0.001). CONCLUSION: In a large population of heart failure patients treated with CRT, the reduction in LV end-systolic volume at the mid-term follow-up demonstrated to be a better predictor of long-term survival than improvement in the clinical status.

Influence of diabetes on left ventricular systolic and diastolic function and on long-term outcome after cardiac resynchronization therapy.

OBJECTIVE: The influence of diabetes on cardiac resynchronization therapy (CRT) remains unclear. The aims of the current study were to 1) assess the changes in left ventricular (LV) systolic and diastolic function and 2) evaluate long-term prognosis in CRT recipients with diabetes. RESEARCH DESIGN AND METHODS: A total of 710 CRT recipients (171 with diabetes) were included from an ongoing registry. Echocardiographic evaluation, including LV systolic and diastolic function assessment, was performed at baseline and 6-month follow-up. Response to CRT was defined as a reduction of ≥15% in LV end-systolic volume (LVESV) at the 6-month follow-up. During long-term follow-up (median = 38 months), all-cause mortality (primary end point) and cardiac death or heart failure hospitalization (secondary end point) were recorded. RESULTS: At the 6-month follow-up, significant LV reverse remodeling was observed both in diabetic and non-diabetic patients. However, the response to CRT occurred more frequently in non-diabetic patients than in diabetic patients (57 vs. 45%, P < 0.05). Furthermore, a significant improvement in LV diastolic function was observed both in diabetic and non-diabetic patients, but was more pronounced in non-diabetic patients. The determinants of the response to CRT among diabetic patients were LV dyssynchrony, ischemic cardiomyopathy, and insulin use. Both primary and secondary end points were more frequent in diabetic patients (P < 0.001). Particularly, diabetes was independently associated with all-cause mortality together with ischemic cardiomyopathy, renal function, LVESV, LV dyssynchrony, and LV diastolic dysfunction. CONCLUSIONS: Heart failure patients with diabetes exhibit significant improvements in LV systolic and diastolic function after CRT, although they are less pronounced than in non-diabetic patients. Diabetes was independently associated with all-cause mortality.

Effect of cardiac resynchronization therapy in patients without left intraventricular dyssynchrony.

AIMS: To evaluate the effects of cardiac resynchronization therapy (CRT) on long-term survival of patients without baseline left ventricular (LV) mechanical dyssynchrony. METHODS AND RESULTS: A total of 290 heart failure patients (age 67 ± 10 years, 77% males) without significant baseline LV dyssynchrony (<60 ms as assessed with tissue Doppler imaging) were treated with CRT. Patients were divided according to the median LV dyssynchrony measured after 48 h of CRT into two groups. All-cause mortality was compared between the subgroups. In addition, the all-cause mortality rates of these subgroups were compared with the all-cause mortality of 290 heart failure patients treated with CRT who showed significant LV dyssynchrony (≥60 ms) at baseline. In the group of patients without significant LV dyssynchrony, median LV dyssynchrony increased from 22 ms (inter-quartile range 16-34 ms) at baseline to 40 ms (24-56 ms) 48 h after CRT. The cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with LV dyssynchrony ≥40 ms 48 h after CRT implantation were significantly higher when compared with patients with LV dyssynchrony <40 ms (10, 17, and 23 vs. 3, 8, and 10%, respectively; log-rank P< 0.001). Finally, the cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with baseline LV dyssynchrony were 3, 8, and 11%, respectively (log-rank P= 0.375 vs. patients with LV dyssynchrony <40 ms). Induction of LV dyssynchrony after CRT was an independent predictor of mortality (hazard ratio: 1.247; P= 0.009). CONCLUSION: In patients without significant LV dyssynchrony, the induction of LV dyssynchrony after CRT may be related to a less favourable long-term outcome.

Implantable cardioverter-defibrillator patients who are upgraded and respond to cardiac resynchronization therapy have less ventricular arrhythmias compared with nonresponders.

OBJECTIVES: The purpose of this study was to evaluate the impact of upgrading implantable cardioverter-defibrillator (ICD) therapy to cardiac resynchronization therapy (CRT) combined with defibrillator (CRT-D) on the occurrence of ventricular arrhythmia (VA) and appropriate ICD therapies. BACKGROUND: CRT has been shown to improve left ventricular (LV) systolic function and induce reverse LV remodeling. In addition, it has been hypothesized that CRT may reduce the incidence of VA. METHODS: Heart failure patients receiving an upgrade from ICD to CRT-D were evaluated. Patients were considered responders to CRT if LV end-systolic volume reduced ≥15% at 6 months of follow-up. Episodes of VA, triggering device therapy (anti-tachycardia pacing and shocks) were recorded before and after upgrade for the overall population. In addition, these outcomes were compared between CRT responders and nonresponders during the follow-up period after CRT response was assessed. RESULTS: One hundred fifteen patients (93 males [81%], age 65 ± 12 years) were evaluated during a mean follow-up of 54 ± 34 months before CRT-D upgrade and 37 ± 27 months after upgrade. In CRT responders (n = 70), the frequency of VA requiring appropriate device therapy demonstrated a trend toward a decrease from 0.51 ± 0.79 to 0.30 ± 0.59 per patient per year after CRT-D upgrade (p = 0.052). In CRT nonresponders (n = 45), the frequency of VA requiring appropriate device therapy significantly increased from 0.40 ± 0.69 to 1.21 ± 2.53 per patient per year after CRT-D upgrade (p = 0.014). CONCLUSIONS: After upgrade from ICD to CRT-D, nonresponders to CRT showed a significant increase in VA burden requiring appropriate device therapy.

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

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

Left ventricular diastolic dyssynchrony assessed with phase analysis of gated myocardial perfusion SPECT: a comparison with tissue Doppler imaging.

PURPOSE: The aim of the current study was to evaluate the feasibility of phase analysis on gated myocardial perfusion SPECT (GMPS) for the assessment of left ventricular (LV) diastolic dyssynchrony in a head-to-head comparison with tissue Doppler imaging (TDI). METHODS: The population consisted of patients with end-stage heart failure of New York Heart Association functional class III or IV with a reduced LV ejection fraction of ≤ 35%. LV diastolic dyssynchrony was calculated using TDI as the maximal time delay between early peak diastolic velocities of two opposing left ventricle walls (diastolic mechanical delay). Significant LV diastolic dyssynchrony was defined as a diastolic mechanical delay of >55 ms on TDI. Furthermore, phase analysis on GMPS was performed to evaluate LV diastolic dyssynchrony; diastolic phase standard deviation (SD) and histogram bandwidth (HBW) were used as markers of LV diastolic dyssynchrony. RESULTS: A total of 150 patients (114 men, mean age 66.0 ± 10.4 years) with end-stage heart failure were enrolled. Both diastolic phase SD (r = 0.81, p < 0.01) and diastolic HBW (r = 0.75, p < 0.01) showed good correlations with LV diastolic dyssynchrony on TDI. Additionally, patients with LV diastolic dyssynchrony on TDI (>55 ms) showed significantly larger diastolic phase SD (68.1 ± 13.4° vs. 40.7 ± 14.0°, p < 0.01) and diastolic HBW (230.6 ± 54.3° vs. 129.0 ± 55.6°, p < 0.01) as compared to patients without LV diastolic dyssynchrony on TDI (≤ 55 ms). Finally, phase analysis on GMPS showed a good intra- and interobserver reproducibility for the determination of diastolic phase SD (ICC 0.97 and 0.88) and diastolic HBW (ICC 0.98 and 0.93). CONCLUSION: Phase analysis on GMPS showed good correlations with TDI for the assessment of LV diastolic dyssynchrony.

Site of latest activation in patients eligible for cardiac resynchronization therapy: patterns of dyssynchrony among different QRS configurations and impact of heart failure etiology.

INTRODUCTION: Cardiac resynchronization therapy (CRT) has emerged as a treatment option for patients with end-stage heart failure and a QRS duration ≥120 ms. Nonetheless, many patients with a prolonged QRS do not demonstrate left ventricular (LV) mechanical dyssynchrony, and discrepancies between electrical and mechanical dyssynchrony have been observed. In addition, several studies demonstrated that superior benefits after CRT could be achieved when the LV pacing lead was positioned at the most delayed myocardial segment. METHODS: A total of 248 heart failure patients scheduled for CRT were included. In all patients, a 12-lead electrocardiogram and 2-dimensional echocardiogram were obtained. Patients were divided into 5 QRS configuration subgroups: narrow, left bundle-branch block, right bundle-branch block, intraventricular conduction delay, and right ventricular pacing. With speckle-tracking radial strain analysis, we evaluated time to peak radial strain. Next, the segments with the least and with the most mechanical activation delay were identified, and LV dyssynchrony was defined as the time delay between the two. RESULTS: Mean QRS duration was 164 ± 31 ms. Mean LV dyssynchrony in all patients was 186 ± 122 ms. Site of latest activation was predominantly located in the lateral (27%), posterior (26%), and inferior (20%) segments. Furthermore, extent of LV dyssynchrony was comparable between QRS configuration subgroups. An unequal distribution of LV segments with the most mechanical delay was observed in the left bundle-branch block and right ventricular pacing subgroups (P < .001 for both), whereas in the narrow, right bundle-branch block, and intraventricular conduction delay subgroups, a more homogeneous distribution was noted. No differences in distribution pattern or in extent of LV dyssynchrony were observed between ischemic and nonischemic heart failure patients. CONCLUSION: The lateral, posterior, and inferior segments take up 73% of the total latest activated segments in heart failure patients eligible for CRT. Presence of LV dyssynchrony can be observed in all QRS configurations. The site of latest activation may be outside the lateral or posterior segment, making echocardiographic assessment of LV dyssynchrony and site of latest activation a valuable technique to optimize patient outcome after CRT.

Comparison of long-term survival of men versus women with heart failure treated with cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an established treatment of patients with heart failure. Several baseline characteristics can influence the CRT outcomes, and little is known about the effect of gender. The aim of the present study was to elucidate the gender-related differences in long-term survival after CRT. A total of 578 consecutive patients with heart failure underwent CRT. At baseline and 6 months after CRT, the clinical and echocardiographic parameters were obtained. All-cause mortality was compared between the men and women. The study population included 431 men (67 ± 9 years) and 147 women (65 ± 11 years). No differences in the clinical and echocardiographic characteristics were observed between the men and women, except for left bundle branch block and a nonischemic etiology of heart failure, which were more frequent in women (81% vs 68% and 63% vs 33%, respectively; p <0.01), and atrial fibrillation, which was more prevalent in men (20% vs 10%, respectively; p = 0.01). During a mean follow-up of 34 ± 25 months, 197 patients died (158 men and 39 women). Kaplan-Meier analysis showed a significant difference in long-term survival between the women and men (p = 0.007). The 2-year all-cause mortality rate was 15% in men and 8% in women (p = 0.025). Cox proportional hazard analysis revealed female gender is an independent predictor of long-term survival, together with heart failure etiology and renal function. In particular, women with heart failure due to a nonischemic etiology showed the best long-term survival rate. In conclusion, female gender and nonischemic etiology were independently associated with better long-term survival after CRT.