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Aims Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Methods and results Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty‐five patients with TTS were split into three subgroups, according to tertiles of C‐reactive protein (CRP) levels at discharge (CRP 19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025). Conclusions Residual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high‐risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.

Introduction Patients with atrial fibrillation (AF) are likely to have multiple co-morbidities and receive anticoagulants after TAVR, which lead to a poor prognosis including bleeding events. Closure time adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test used as a surrogate marker of high molecular weight (HMW) multimers defect of Von Willebrand factor (VWF). Our prior studies suggest that prolongation of CT-ADP (>180 seconds) after TAVR is a major determinant of early and late major/life-threatening bleeding complications (MLBCs). Purpose To evaluate the impact of post-procedural CT-ADP >180sec on bleeding events in AF patients. Methods We included 878 patients from our prospective TAVR registry between 2010 and 2019. Bleeding complications were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year after TAVR. Ongoing primary haemostasis disorder was defined by post-procedure CT-ADP >180sec. Primary endpoint was the occurrence of MLBCs during the first year and the second endpoint was 1-year MACCE. Results Patients with AF had a higher incidence of all-cause mortality (15% vs. 8%, p=0.002), MACCE (29% vs. 20%, p=0.002), and MLBCs (20% vs. 12%, p=0.001) within 1-year compared to non-AF patients. When the cohort was split into 4 subgroups according to AF and CT-ADP >180sec, patients with AF and CT-ADP >180sec had the highest risk of MLBCs (log-rank test; p180sec had 4.6-fold higher risk of MLBCs within 1 year compared to non-AF patients with CT-ADP ≤180sec (hazard ratio: 4.60; 95% confidence interval: 2.18 - 9.68; p Conclusion Among TAVR patients, AF with post-procedural CT-ADP >180 sec was identified as a strong independent predictor of MLBCs at 1-year follow-up. Our study suggest that persistent primary haemostasis disorders contribute to a higher risk of bleeding events particularly in AF patients and may be considered for a tailored and risk-adjusted antithrombotic therapy after TAVR. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Matsushita received a grant from Edwards Lifesciences.

Background Electrocardiographic strain pattern (ESP) has recently been associated with increased adverse outcome in aortic stenosis and after surgical aortic valve replacement. Our study sought to determine the impact and incremental value of ESP pattern in predicting adverse outcome after transcatheter aortic valve replacement. Methods and Results A total of 585 patients with severe aortic stenosis (mean age, 83±7 years; men, 39.8%) were enrolled for transcatheter aortic valve replacement from November 2012 to May 2018. ESP was defined as ≥1‐mm concave down‐sloping ST‐segment depression and asymmetrical T‐wave inversion in the lateral leads. The primary end points of the study were all‐cause mortality, rehospitalization for heart failure, myocardial infarction, and stroke. A total of 178 (30.4%) patients were excluded because of left bundle‐branch block (n=103) or right bundle‐branch block (n=75). Among the 407 remaining patients, 106 had ESP (26.04%). At a median follow‐up of 20.00 months (11.70–29.42 months), no impact of electric strain on overall and cardiac death could be established. By contrast, incidence of rehospitalization for heart failure was significantly higher (33/106 [31.1%] versus 33/301 [11%]; P P Conclusions In patients with aortic stenosis who were eligible for transcatheter aortic valve replacement, ESP is frequent and associated with an increased risk of postinterventional heart failure regardless of preoperative left ventricular hypertrophy. ESP represents an easy, objective, reliable, and low‐cost tool to identify patients who may benefit from intensified postinterventional follow‐up.

Background Coronary artery disease (CAD) has been recognized as a major determinant of Covid-19 vulnerability and severity. We sought to compare demographic characteristics, clinical presentation, and outcomes for Covid-19 in a large cohort of chronic CAD patients living in Strasbourg's cluster region ( Fig. 1 ). Methods Follow-up was conducted by telephone interviews performed by cardiologists one month after the start of the French lockdown. The primary outcome was the composite of death or hospitalization related to Covid-19 infection. Secondary endpoints included Covid-19 related death, Covid-19 related hospitalization, intensive care unit (ICU) admission, allcause mortality, cardiovascular (CV) mortality and healthcare compliance. Results Out of 891 patients included, twenty CAD patients (2.2%) had RT-PCR confirmed Covid-19 infection. Confirmed or suspect cases were evidenced in 48 patients (5.4%). Covid-19 patients showed lower left ventricular ejection fraction, were more frequently obese, less likely to smoke or follow lipid lowering therapy. The composite of death or hospitalization related to Covid-19 was 90%. Mortality rate was 30% among confirmed Covid-19 patients. Drugs’ discontinuation rate was low (1.1%) during the confinement. Reticence to consult a healthcare professional occurred in 6.4%. Postponement or cancellation of non-essential medical visits occurred in 15,7% ( Table 1 ). Conclusions Coronary patients from a large French cluster of COVID-19 showed a high risk of Covid-19 infection and worse in-hospital outcomes.

Background Acute kidney injury (AKI) is associated with a dismal prognosis in Transcatheter Aortic Valve replacement (TAVR). Acute kidney recovery (AKR), a phenomenon reverse to AKI has recently been associated with better outcomes. Methods Between November 2012 to May 2018, we explored consecutive patients referred to our Heart Valve Center for TAVR. AKI was defined according to the VARC-2 definition. Mirroring the VARC-2 definition of AKI, AKR was defined as a decrease in serum creatinine (≥50%) or ≥25% improvement in GFR up to 72 hours after TAVR. Results AKI and AKR were respectively observed in 8.3 and 15.7% of the 574 patients included. AKI and AKR patients were associated to more advanced kidney disease at baseline. At a median follow-up of 608 days (range 355–893), AKI and AKR patients experienced an increased cardiovascular mortality compared to unchanged renal function patients (14.6% and 17.8% respectively, vs. 8.1%, CI 95%, pp < 0.001) was the strongest independent factor associated with AKI similarly to baseline creatinine level (HR: 1; 95% CI 1 to 1.1 p < 0.001) for AKR. 72-hours post procedural AKR (HR: 2.26; 95% CI 1.14 to 4.88; p = 0.021) was the strongest independent predictor of CV mortality. Conclusions Both AKR and AKI negatively impact long term clinical outcomes of patients undergoing TAVR.

Introduction Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with takotsubo cardiomyopathy, recent studies have demonstrated the long-lasting functional impairment in those patients. Purpose We sought to evaluate the predictors of incomplete recovery in chronic phase and its impact on cardiovascular mortality after takotsubo cardiomyopathy. Methods Patients with takotsubo cardiomyopathy between 2008 and 2018 were retrospectively enrolled in three different institutions. Takotsubo cardiomyopathy was diagnosed according to the European Society of Cardiology Heart Failure Association criteria. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according whether their LVEF were >50% (recovery group; n=333), or ≤50% (incomplete recovery group; n=74) at follow-up. The primary endpoint was the impact of incomplete recovery on cardiovascular mortality. Results Patients with incomplete recovery were more likely to be male, to have dementia, pacemaker, and supraventricular arrhythmia. C-reactive protein (CRP) levels on admission, at peak, and at discharge were significantly higher in patients with incomplete recovery. By multivariate logistic regression analysis, lower EF at discharge (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.88 to 0.95; p Conclusions We demonstrate that incomplete recovery after takotsubo cardiomyopathy is characterized by a residual systemic inflammation and an increased cardiac mortality at follow-up. Altogether, our findings underline patients with persistent inflammation as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate inflammation. Funding Acknowledgement Type of funding source: None

Introduction Current recommendations support short-term dual antiplatelet therapy (DAPT) for patients undergoing transcatheter aortic valve replacement (TAVR) despite no relevant study exploring the extent of platelet inhibition by clopidogrel. Purpose To assess whether P2Y12 inhibition by clopidogrel as evaluated by vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) impacts 1-year clinical outcomes in patients undergoing TAVR. Methods Patients were included in a prospective registry between February 2010 and May 2019. VASP-FCT was assessed 24h after the procedure. Responder to clopidogrel was defined by a platelet reactivity index ≤50%. Results Of 640 patients who underwent TAVR with preprocedural clopidogrel therapy, we enrolled 491 patients for whom VASP data were available. Responders were identified in 22% (n=110) of patients and low responders were 78% (n=381) of patients. Low body mass index, active cancer, and clopidogrel on admission were found to be independent predictors of responder. Mean transaortic pressure gradient was lower in the responder group at 1-month post-TAVR (9.9±4.4 mmHg vs. 11.2±5.8 mmHg, p=0.03) but was similar at 1-year (11.5±6.2 mmHg vs. 11.9±7.4 mmHg, p=0.74). By multivariate Cox regression analysis, patients responding to clopidogrel (hazard ratio [HR]: 2.19; 95% confidence interval [CI]: 1.04 to 3.64; p=0.04), prior PCI (HR: 2.12; 95% CI: 1.07 to 4.37; p=0.03), and mean transaortic pressure gradient at baseline (HR: 0.07; 95% CI: 0.01 to 0.70; p=0.02) were identified as independent predictors of 1-year adverse clinical outcomes, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization. Conclusions Appropriate P2Y12 inhibition by clopidogrel is a major determinant of adverse clinical events after TAVR. In sum, the present data challenges the need of DAPT as a standard therapy during TAVR. Figure 1 Funding Acknowledgement Type of funding source: None

Introduction Paravalvular leakage (PVL) following transcatheter aortic valve replacement (TAVR) is associated with greater mortality. In clinical practice, determining PVL severity after TAVR remains challenging and often requires multiparametric assessment. Purpose This study sought to evaluate the respective value of various modalities of PVL assessments, including transthoracic echocardiography (TTE), cine-angiography, aortic regurgitation index (ARI), and closure time with adenosine diphosphate (CT-ADP), in the prediction of adverse clinical outcomes. Methods We included 1044 patients from our prospective TAVR registry between February 2010 and May 2019. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year. Established cutoff values of ARI (180 sec) were used to assess the presence of PVL after TAVR. Results Moderate to severe PVL occurred in 14.2% and 5.2% of patients as measured by TTE and angiography. The rate of patients with ARI 180 sec were 36.5% and 24.9%, respectively. Among the four modalities, PVL evaluated by angiography predicted poorer clinical outcomes (Log rank test; p=0.001), whereas TTE, ARI 180 sec were not associated with 1-year MACCE. By multivariate Cox regression analysis, moderate to severe PVL by angiography was an independent predictor of 1-year MACCE (hazard ratio: 1.96; 95% confidence interval: 1.22–3.00; p=0.007). Conclusions Paravalvular leakage measured by angiography was evidenced as the most meaningful modality in the prediction of adverse clinical outcomes. Future multicenter studies are warranted to ensure these findings in the current TAVR era. Figure 1 Funding Acknowledgement Type of funding source: None

AIMS: Cardiovascular disease has been recognized as a major determinant of coronavirus disease 2019 (COVID-19) vulnerability and severity. Angiotensin-converting enzyme (ACE) 2 is a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is up-regulated in patients with heart failure. We sought to examine the potential association between reduced left ventricular ejection fraction (LVEF) and the susceptibility to SARS-CoV-2 infection. METHODS AND RESULTS: Of the 1162 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention between February 2014 and October 2018, we enrolled 889 patients with available clinical follow-up data. Follow-up was conducted by telephone interviews 1 month after the start of the French lockdown which began on 17 March 2020. Patients were divided into two groups according to LVEF 60;40% (reduced LVEF) (n = 91) or ≥40% (moderately reduced + preserved LVEF) (n = 798). The incidence of COVID-19-related hospitalization or death was significantly higher in the reduced LVEF group as compared with the moderately reduced + preserved LVEF group (9% vs. 1%, P 60; 0.001). No association was found between discontinuation of ACE-inhibitor or angiotensin-receptor blockers and COVID-19 test positivity. By multivariate logistic regression analysis, reduced LVEF was an independent predictor of COVID-19 hospitalization or death (odds ratio: 6.91, 95% confidence interval: 2.60 to 18.35, P 60; 0.001). CONCLUSIONS: In a large cohort of patients with previous ACS, reduced LVEF was associated with increased susceptibility to COVID-19. Aggressive COVID-19 testing and therapeutic strategies may be considered for patient with impaired heart function.

Background New-onset conduction abnormalities (CAs) following transcatheter aortic valve replacement (TAVR) are associated with hospital rehospitalization and long-term mortality, but available predictors are sparse. This study sought to determine clinical predictors of new-onset left bundle branch block (LBBB) and new permanent pacemaker (PPM) implantation in patients undergoing TAVR.Methods and Results:We enrolled 290 patients who received SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA; n=217) or Evolut R (Medtronic, Minneapolis, MN, USA; n=73) from a prospective registry at Nouvel Hopital Civil, Strasbourg, France between September 2014 and February 2018. Of 242 patients without pre-existing LBBB, 114 (47%) experienced new-onset LBBB and/or new PPM implantation. A difference between membranous septal length and implantation depth (∆MSID) was the only predictor of CAs for both types of valves. In the multivariate analysis, PR interval and ∆MSID remained as sole predictors of CAs. The risk for adverse clinical events, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization, was higher for patients with CAs as compared with patients without CAs (hazard ratio: 2.10; 95% confidence interval: 1.26 to 3.57; P=0.004). Conclusions Computed tomography assessment of membranous septal anatomy and implantation depth predicted CAs after TAVR with new-generation valves. Future studies are required to identify whether adjustment of the implantation depth can reduce the risk of CAs and adverse clinical outcomes.

Background Stroke is a major cause of disability after transcatheter aortic valve replacement (TAVR) and stroke prediction models and data are crucially needed. Following TAVR, high molecular weight (HMW) multimers defect of von Willebrand factor (VWF) as assessed by closure time of adenosine diphosphate (CT-ADP) value > 180 seconds is an independent predictor of bleeding events. This study sought to identify predictors of ischemic neurological events in patients who underwent TAVR and the specific impact of HMW multimers defect of VWF. Methods Patients were prospectively enrolled between November 2012 and May 2018 at our institution. The CT-ADP, a point-of-care measure of hemostasis, was assessed the day before and 24 hours after the procedures. The rate of ischemic stroke and transient ischemic attack (TIA) was recorded up to 30 days after the procedures. Results Of 565 TAVR patients, ischemic stroke/TIA was observed in 21 (3.7%) patients within 30 days. Ischemic stroke/TIA was associated with major/life-threatening bleeding complications (MLBCs) (9 [43%] vs. 88 [16%], p = 0.002) and postprocedure CT-ADP > 180 seconds (10 [48%] vs. 116 [21%], p = 0.01). By multivariate analysis, MLBCs (odds ratio [OR]: 3.58; 95% confidence interval [CI]: 1.45–8.84; p = 0.006) and postprocedure CT-ADP > 180 seconds (OR: 3.38; 95% CI: 1.38–8.25; p = 0.008) were evidenced as independent predictors of ischemic stroke/TIA. Conclusion MLBCs and CT-ADP > 180 seconds were identified as predictors for ischemic stroke or TIA. The present study suggests that the defects of HMW multimers of the VWFs may contribute not only to bleeding events but also to thrombotic events.

Background: The impact of coronary artery disease (CAD) and revascularization by percutaneous coronary intervention (PCI) on prognosis in patients undergoing transcatheter aortic valve replacement (TAVR) remain debated. A dismal prognosis in patients undergoing PCI has been associated with elevated baseline SYNTAX score (bSS) and residual SYNTAX score (rSS). The objective was to investigate whether the degree of bSS and rSS impacted ischemic and bleeding events after TAVR. Methods: bSS and rSS were calculated in 311 patients admitted for TAVR. The primary outcome was the occurrence of major adverse cardiac events (MACE), a composite endpoint of myocardial infarction, stroke, cardiovascular death, or rehospitalization for heart failure. The occurrence of late major/life-threatening bleeding complications (MLBCs) and each primary endpoint individually were the secondary endpoints. Results: bSS &gt, 22 was associated with higher occurrence of MACE (p = 0.013). rSS &gt, 8 and bSS &gt, 22 had no impact on overall cardiovascular mortality. rSS &gt, 22 were associated with higher rates of myocardial infarction (p = 0.001 and p = 0.004) and late occurrence of MLBCs. Multivariate analysis showed that bSS &gt, 22 (sHR 2.48) and rSS &gt, 8 (sHR 2.35) remained predictors of MLBCs but not of myocardial infarction. Conclusion: Incomplete coronary revascularization and CAD burden did not impact overall and cardiac mortality but constitute predictors of late MLBCs in TAVR patients.

Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is associated with a dismal prognosis. Elevated renal resistive index (RRI), through renal Doppler ultrasound (RDU) evaluation, has been associated with AKI development and increased systemic arterial stiffness. Our pilot study aimed to investigate the performance of Doppler based RRI to predict AKI and outcomes in TAVR patients. From May 2018 to May 2019, 100 patients with severe aortic stenosis were prospectively enrolled for TAVR and concomitant RDU evaluation at our institution (Nouvel H&ocirc, pital Civil, Strasbourg University, France). AKI by serum Creatinine (sCr-AKI) was defined according to the VARC-2 definition and AKI by serum Cystatin C (sCyC-AKI) was defined as an sCyC increase of greater than 15% with baseline value. Concomitant RRI measurements as well as renal and systemic hemodynamic parameters were recorded before, one day, and three days after TAVR. It was found that 10% of patients presented with AKIsCr and AKIsCyC. The whole cohort showed higher baseline RRI values (0.76 &plusmn, 0.7) compared to normal known and accepted values. AKIsCyC had significant higher post-procedural RRI one day (Day 1) after TAVR (0.83 &plusmn, 0.1 vs. 0.77 &plusmn, 0.6, CI 95%, p = 0.005). AUC for AKIsCyC was 0.766 and a RRI cut-off value of &ge, 0.795 had the most optimal sensitivity/specificity (80/62%) combination. By univariate Cox analysis, Mehran Risk Score, higher baseline right atrial pressure at baseline &gt, 0.8 RRI values one day after TAVR (HR 6.5 (95% CI 1.3&ndash, 32.9, p = 0.021) but not RRI at baseline were significant predictors of AKIsCyC. Importantly, no significant impact of baseline biological parameters, renal or systemic parameters could be demonstrated. Doppler-based RRI can be helpful for the non-invasive assessment of AKI development after TAVR.

Background Dual antiplatelet therapy (DAPT) has been proposed to explain the increased occurrence of major bleeding events after transcatheter aortic valve replacement (TAVR) despite no relevant study exploring the extent of platelet inhibition by clopidogrel. Purpose To assess whether P2Y12 inhibition by clopidogrel as evaluated by vasodilator-stimulated phosphoprotein (VASP) flow cytometry test impacts clinical outcomes in patients undergoing TAVR. Methods Patients were enrolled in a prospective registry at Nouvel Hopital Civil, Strasbourg, France between February 2010 and May 2019. VASP flow cytometry test was assessed 24 h after the procedure. Responder to clopidogrel was defined by a platelet reactivity index ≤ 50%. The primary endpoint was 90-day major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, stroke, and heart failure hospitalization. The secondary endpoint was 1-year MACCE. Results Of the 828 patients with available VASP monitoring, we enrolled 491 TAVR patients with preprocedural clopidogrel therapy. Responders were identified in 22% (n = 110) and low responders in 78% (n = 381) of patients. By multivariate Cox regression analysis, patients responding to clopidogrel (hazard ratio [HR]: 2.16; 95% confidence interval [CI]: 1.16 to 3.91: P = 0.02) and previous PCI (HR: 2.24; 95% CI: 1.07 to 4.81; P = 0.03) were identified as independent predictors of 90-day MACCE. The cumulative event-free survival rate at 90-day and 1-year was significantly lower in the responder group ( Fig. 1 ). Conclusions Appropriate P2Y12 inhibition by clopidogrel is a major determinant of 90-day and 1-year post-TAVR adverse clinical events. In sum, the present data challenge DAPT as a standard therapy during TAVR.

Background The respective influences of coronary artery disease (CAD) and revascularization by percutaneous coronary intervention (PCI) on prognosis in patients undergoing Transcatheter aortic-valve replacement (TAVR) remain highly controversial. The residual SYNTAX Score (rSS) has been developed to assess the impact of residual CAD after PCI. Both baseline SYNTAX Score (bSS) and rSS have been associated with dismal prognosis in patients undergoing PCI. Objectives To assess whether the degree of bSS and rSS impact ischemic and bleeding events after TAVR. Method Three hundred and eleven patients were admitted for TAVR. Severe CAD was defined by bSS > 22. Incomplete revascularization was defined by rSS > 8. The primary outcome was the occurrence of a composite endpoint of either cardiovascular death, myocardial infarction, stroke or rehospitalization for heart failure (MACE). Secondary endpoints included each primary endpoint individually and the occurrence of late major/life threatening bleeding complications (MLBCs). Results After a median follow-up of 830 days, bSS > 22 was associated with higher occurrence of MACE (P = 0.013). However, bSS > 22 and rSS > 8 had no impact on overall cardiovascular mortality. By contrast, they were associated with higher rates of periprocedural major bleeding (P = 0.002), myocardial infarction (P = 0.001) and late occurrence of MLBCs and transfusion rate (P = 0.005). Results of multivariate analysis showed that bSS > 22 (HR 2.43 95% CI (1.01–5.85); P = 0.048) and rSS > 8 (HR 2.39 95% CI (1.2–4.7); P = 0.013) remained predictors of MLBCs but not of myocardial infarction ( Table 1 , Fig. 1 ). Conclusion In unselected TAVR patients, initial CAD burden and incomplete coronary revascularization did not impact overall and cardiac mortality but constitute reliable predictors of late MLBCs.

Background The impact of antithrombotic regimen and platelet inhibition extent on subclinical leaflet thrombosis (SLT) detected by cardiac multidetector computed tomography (MDCT) after transcatheter aortic-valve replacement (TAVR) is not well established. Hypoattenuation affecting motion (HAM) has been proposed as a surrogate marker of SLT and is characterized by hypoattenuated leaflet thickening (HALT) and concomitant reduction in leaflet motion (RELM). Purpose We sought to investigate (i) the prevalence of HAM and HALT, (ii) the predictors of SLT, (iii) the impact of oral anticoagulant (OAC), platelet inhibition extent and primary haemostasis disorders on SLT. Methods Of 187 consecutive patients who underwent TAVR from August 1st 2017 to March 31th 2018, 90 of them had cardiac CT at relevant follow-up. Clinical, biological, echocardiographic, procedural characteristics and treatments were collected before, at discharge and 1 year after TAVR. P2Y12 platelet inhibition extent and primary haemostasis disorders were investigated using platelet PRI-VASP and CT-ADP point of care assays. Results Eighty five post-TAVR CTs out of 90 were ranked for clarity. HAM was evidenced in 13 patients (15%) and HALT in 30 patients (35%). No impact of P2Y12 inhibition nor primary haemostasis disorders on SLT could be evidenced. No impact of SLT on valve deterioration evaluated by transthorac echocardiography (TTE) and clinical events could be established at 12 months follow-up. By multivariate analysis, lack of oral anticoagulant therapy at discharge (HR 12.130 CI 95% [1.394–150.582]; P = 0.028) and higher haemoglobin levels were evidenced as independent predictors of SLT. In 4 patients with HAM, MDCT follow-up after initiation of OAC therapy showed a complete regression of HAM ( Fig. 1 ). Conclusion SLT was evidenced in a sizeable proportion of patients after TAVR and was mainly determined by the lack of oral anticoagulant therapy. No impact of platelet inhibition extent on SLT could be evidenced.

Background Cardiovascular diseases and cancer are the two leading causes of mortality in the world and their association is a therapeutic challenge. Current data showed that patients with active cancer and severe aortic stenosis have better survival after aortic-valve replacement in comparison with those have medical treatment. Presence of active cancer is frequently a reason to decline surgery due to the fear of periprocedural complications in this frail population and transcatheter aortic-valve replacement (TAVR) appears like the treatment of choice in this situation. However, data concerning outcomes in this case are limited and contradictory. Purpose This study aims to constitute the first French cohort of patients with active cancer undergoing TAVR in order to determine their prevalence, characteristics, perioperative outcomes and mortality. Methods We prospectively included all consecutive patients who underwent TAVR in our institution (Nouvel Hopital Civil, Strasbourg, France). Active cancer status at the time of the procedure was determined by a specialist physician with an anatomopathological diagnosis in all cases where it was possible. Primary endpoint was all-cause mortality during follow-up. Results Among 585 patients who underwent TAVR, 62 had an active cancer. All-cause mortality was significantly higher in patients with active cancer in comparison with those without cancer (38.7% vs. 20.1% respectively; P = 0.001). This excess of mortality is mainly driven by non-cardiovascular causes of death. Other periprocedural complications (major adverse cardiovascular events, bleeding, rehospitalization for heart failure, acute kidney injury) did not differ between the two groups ( Fig. 1 ). Conclusion In patients who underwent TAVR, active cancer is a non-negligible comorbidity. All-cause mortality is higher in this population, mainly driven by non-cardiovascular mortality. However, periprocedural complications are not increased in this specific population.

Background Electrocardiographic (ECG) strain pattern has recently been associated with increased adverse outcome in aortic stenosis (AS) and after surgical aortic valve replacement (AVR). However, the relation linking ECG strain and cardiovascular MACE in patients with transcatheter aortic valve replacement (TAVR) has not been yet described. Objectives The aim of our study was to determine the impact and incremental value of ECG Strain pattern in predicting adverse outcome after TAVR. Methods 585 patients with severe AS (mean age: 83±7 male 39.8%) were enrolled from November 2012 to May 2018. ECG strain pattern was defined as ≥1 mm concave down-sloping ST-segment depression and asymmetrical T-wave inversion in the lateral leads. Patients with baseline left bundle branch block (LBBB), right bundle branch block (RBBB) or ventricular paced rhythm were excluded. All patients underwent transthoracic echocardiography (TTE) before TAVR and at 30 days follow up. The primary endpoints of the study were the overall all-cause mortality after TAVR, rehospitalization for Hearth failure (HF), myocardial infarction and stroke. Results 178 (30.4%) patients were excluded from analyses owing to the presence of either LBBB (n=103) or RBBB (n=75). Among the 407 remaining patients, 106 had ECG strain pattern (26.04%). Patients with ECG strain were significantly younger (81.6±8 years vs 83.5±6.8 years; p=0.022), had lower BMI (23±4.5 kg.m2 vs 27.9±6.8 kg.m2; p=0.02) more severe AS (mean gradient 52.3±15.2 mmHg vs 47.9±11.8 mmHg; p=0.003), significant lower LVEF (51.8±15% vs 58.4±10.7%; p Conclusion In patients with AS eligible for TAVR, ECG Strain Pattern is frequent and associated with an increased risk of post interventional heart failure regardless of preoperative LVH. ECG Strain pattern represents an easy, objective, reliable and low-cost tool to identify patients who may benefit from an extend and intensified post-interventional follow-up.

Background and purpose Acute kidney injury (AKI) remains associated with a dismal prognosis in TAVR. Acute kidney recovery (AKR), a phenomenon reverse to AKI has recently been associated with better outcomes. Methods Between November 2012 to May 2018, we explored consecutive patients referred to our Heart Valve Center for TAVR. AKI was defined according to the VARC-2 definition. Mirroring the VARC-2 definition of AKI, AKR was defined as a decrease in serum creatinine (≥ 50%) or ≥ 25% improvement in GFR up to 72 hours after TAVR. Results AKI and AKR were respectively observed in 8.3 and 15.7% of the 574 patients included. AKI and AKR patients were associated to more advanced kidney disease at baseline. At a median follow-up of 608 days (range 355–893), AKI and AKR patients experienced an increased cardiovascular mortality compared to unchanged renal function patients (14.6% and 17.8% respectively, vs. 8.1%, CI 95%, P Fig. 1 ). Conclusions 72-hours post procedural AKR patients are a subgroup of patients at high risk of post TAVR cardiovascular complications

Background Electrocardiographic (ECG) strain pattern (ESP) has recently been associated with increased adverse outcome in aortic stenosis (AS) and after surgical aortic-valve replacement (AVR). However, the relation linking ESP and cardiovascular MACE in patients with transcatheter aortic-valve replacement (TAVR) has not been yet described. Objectives Our study sought to determine the impact and incremental value of ESP pattern in predicting adverse outcome after TAVR. Methods A total of 585 patients with severe AS (mean age: 83 ± 7 years; male 39.8%) were enrolled for TAVR from November 2012 to May 2018. ESP was defined as ≥ 1 mm concave down-sloping ST-segment depression and asymmetrical T-wave inversion in the lateral leads. Patients with baseline left bundle branch block (LBBB), right bundle branch block (RBBB) or ventricular paced rhythm were excluded. The primary endpoints of the study were the overall all-cause mortality after TAVR, rehospitalization for hearth failure (HF), myocardial infarction and stroke. Results 178 (30.4%) patients were excluded owing to LBBB (n = 103) or RBBB (n = 75). Among the 407 remaining patients, 106 had ESP (26.04%). Patients with ESP were younger, had lower BMI and more severe AS and significant lower LVEF. At a median follow-up of 608 days (356–895), no impact of electric strain on overall and cardiac death could be established. By contrast, incidence of rehospitalization for HF was significantly higher (33 (31.1%) vs. 33 (11%); P Conclusion In patients with AS eligible for TAVR, ESP is frequent and associated with an increased risk of post interventional heart failure regardless of preoperative LVH. ESP represents an easy, objective, reliable and low-cost tool to identify patients who may benefit from intensified post-interventional follow-up.

The impact of antithrombotic regimen and platelet inhibition extent on subclinical leaflet thrombosis (SLT) detected by cardiac multidetector computed tomography (MDCT) after transcatheter aortic valve replacement (TAVR) is not well established. Hypoattenuation affecting motion (HAM) has been proposed as a surrogate marker of SLT, and is characterized by hypoattenuated leaflet thickening (HALT) and concomitant reduction in leaflet motion (RELM). We sought to investigate (i) the prevalence of HAM and HALT after TAVR detected by MDCT, (ii) the predictors of SLT, (iii) the impact of oral anticoagulant (OAC) and platelet inhibition extent assessed by platelet reactivity index vasodilator stimulated phosphoprotein (PRI-VASP) and closure time adenosine diphosphate (CT-ADP) on SLT. Of 187 consecutive patients who underwent TAVR from 1 August 2017 to 31 March 2018, 90 of them had cardiac CT at relevant follow-up. Clinical, biological, echocardiographic, procedural characteristics and treatments were collected before, at discharge, and 1 year after TAVR. P2Y12 platelet inhibition extent and primary haemostasis disorders were investigated using platelet PRI-VASP and CT-ADP point-of-care assays. Eighty-five post-TAVR CTs out of 90 were ranked for clarity and assessed with sufficient diagnostic quality. HAM was evidenced in 13 patients (15.3%) and HALT in 30 patients (35%). Procedural characteristics, including aortic valve calcium score, annulus size, or procedural heparin regimens, were equivalent between groups. Likewise, no impact of P2Y12 inhibition (PRI-VASP) nor primary haemostasis disorders (CT-ADP) on SLT could be evidenced. No impact of SLT on valve deterioration evaluated by transthoracic echocardiography (TTE) and clinical events could be established at 12 months follow-up. By multivariate analysis, lack of oral anticoagulant therapy at discharge (HR 12.130 CI 95% (1.394&ndash, 150.582), p = 0.028) and higher haemoglobin levels were evidenced as the sole independent predictors of SLT. In four patients with HAM, MDCT follow-up was obtained after initiation of OAC therapy and showed a complete regression of HAM. SLT was evidenced in a sizeable proportion of patients treated by TAVR and was mainly determined by the lack of oral anticoagulant therapy. Conversely, no impact of platelet inhibition extent on SLT could be evidenced.

Background Hypotensive states that require fast stabilisation of blood pressure can occur during anaesthesia. In 1963, the 20:1 mixture of cafedrine/theodrenaline (Akrinor®) was introduced in Germany for use in anaesthesia and emergency medicine in the first-line management of hypotensive states. Though on the market for many years, few pharmacodynamic data are available on this combination net beta-mimetic agent. Aim This study aimed to examine the drug combination in real-life clinical practice and recorded time to 10 % mean arterial blood pressure (MAP) increase and heart rate. Furthermore, potential factors that influence drug effectiveness under anaesthesia were assessed. Methods Data were collected within a standardised anaesthesia protocol. A total of 353 consecutive patients (female/male = 149/204) who received cafedrine/theodrenaline after a drop in MAP ≥ 5 % were included in the study. The time to 10 % increase in MAP, dosage of cafedrine/theodrenaline, volume loading, blood pressure and heart rate were monitored over time. Results Patients were a mean (standard deviation) of 64.4 ± 15.1 years old with a baseline MAP of 82 ± 14 mmHg, which dropped to a mean of 63 ± 10 mmHg during anaesthesia without gender differences. Cafedrine/theodrenaline (1.27 ± 1.0 mg/kg; 64 ± 50 µg/kg) significantly increased MAP (p

Thrombolytic therapy salvages ischemic myocardium by rapidly reestablishing coronary artery patency in acute myocardial infarction. One of its major limitations is the complication of hemorrhage. A retrospective study of myocardial infarction patients who received thrombolytic therapy was performed to determine risk factors associated with a hemorrhagic event. Three hundred fifty patients were enrolled, and 20 (5.7%) had a bleeding complication, including four patients (1.1%) who had an intracranial hemorrhage. The factors associated with an increased risk for a significant hemorrhagic event were age (>65 years) and female gender. Factors associated with an intracranial hemorrhage were age (>65 years) and a history of hypertension.

The incidence and clinical predictors of amiodarone pulmonary toxicity were examined in 573 patients treated with amiodarone for recurrent ventricular (456 patients) or supraventricular (117 patients) tachyarrhythmias. Amiodarone pulmonary toxicity was diagnosed in 33 of the 573 patients (5.8%), based on symptoms and new chest radiographic abnormalities (32 of 33 patients) and supported by abnormal pulmonary biopsy (13 of 14 patients), low pulmonary diffusion capacity (DLCO) (nine of 13 patients), and/or abnormal gallium lung scan (11 of 16 patients). Toxicity occurred between 6 days and 60 months of treatment for a cumulative risk of 9.1%, with the highest incidence occurring during the first 12 months (18 of 33 patients). Older patients developed it more frequently (62.7 +/- 1.7 versus 57.4 +/- 0.5 years, p = 0.018), with no cases diagnosed in patients who started therapy at less than 40 years of age. Gender, underlying heart disease, arrhythmia, and pretreatment chest radiographic, spirometric, or lung volume abnormalities did not predict development of amiodarone pulmonary toxicity, whereas pretreatment DLCO was lower in the group developing it (76.0 +/- 5.5% versus 90.4 +/- 1.4%, p = 0.01). There was a higher mean daily amiodarone maintenance dose in the pulmonary toxicity group (517 +/- 25 versus 409 +/- 6 mg, p less than 0.001) but no difference in loading dose. No patient receiving a mean daily maintenance dose less than 305 mg developed pulmonary toxicity. Patients who developed toxicity had higher plasma desethylamiodarone (2.34 +/- 0.18 versus 1.92 +/- 0.04 micrograms/ml, p = 0.009) but not amiodarone concentrations during maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Between 1977 and 1986, 589 patients (age, 57 +/- 13 years; 464 men and 125 women) received amiodarone for ventricular fibrillation (VF; 147 patients), sustained (VT-S; 242 patients) or nonsustained (VT-NS; 80 patients) ventricular tachycardia, or supraventricular tachycardia (SVT; 120 patients). Mean left ventricular ejection fraction was 36 +/- 17%, with 23% in New York Heart Association functional class I, 49% in class II, 25% in class III, and 3% in class IV. Sixty-two percent had ischemic heart disease. Follow-up was 32 +/- 27 months (mean +/- SD). Life table analysis revealed that patients with VF, VT-S, and VT-NS had a cumulative incidence of sudden death of 9% at 1 year, increasing by about 3% per year. By years 2 and 5, the cumulative incidence of sudden death, VF, or VT-S recurrence was 26% and 38% and the percent of patients still taking amiodarone was 54% and 32%. For patients with SVT at years 2 and 5, the cumulative incidence of sudden death was 1% and 3%, and of sudden death or SVT recurrence the cumulative incidence was 20% and 29%. The percent of patients still taking amiodarone was 67% and 43%. Of 14 clinical variables assessed, New York Heart Association functional class was the best predictor of sudden death and arrhythmic failure and no other variable added independent predictive power. Older age and lower left ventricular ejection fraction were independent predictors of drug failure (sudden death or arrhythmic failure or need to discontinue amiodarone because of side effects). We conclude that despite its side effect profile, amiodarone is an effective and reasonably well-tolerated antiarrhythmic drug.

The site of ventricular stimulation is an important variable in the initiation of ventricular tachycardia (VT) by programmed ventricular stimulation. Among 169 patients studied consecutively, 17 (10%) had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex. Fourteen of these 17 patients had had prior myocardial infarction (12 had inferior, and two had both inferior and anterior myocardial infarction), two had a dilated cardiomyopathy, and one had a localized cardiomyopathy. Fourteen patients had echocardiograms suitable for analysis. Of these, 12 had posterior/inferior ventricular wall motion abnormalities located at the base of the heart. The ventricular effective refractory periods from the right ventricular outflow tract and right ventricular apex were 237 +/- 4 and 244 +/- 5 msec, respectively (p less than 0.05, mean +/- SEM). Induced VT had a cycle length of 229 +/- 4 msec and had the morphology of right bundle branch block in 12 patients, of left bundle branch block in three patients, and had both morphologies in two patients. In 14 patients the axis was superior. VT was initiated with two extrastimuli in 15 patients and with burst right ventricular pacing in two patients. Similar pacing techniques with identical pacing intervals did not induce VT at the right ventricular apex in 14 of these 17 patients. Further, among the 15 patients whose VT was induced at the right ventricular outflow tract with two extrastimuli, neither burst pacing (n = 13) nor two extrastimuli introduced at faster paced rates (n = 12) induced VT at the right ventricular apex.(ABSTRACT TRUNCATED AT 250 WORDS)

We followed 11 patients for 5 to 27 months (mean 14.9) after implantation of a permanent transvenous low-energy synchronized cardioverter to evaluate both long-term reproducibility of ventricular tachycardia (VT) induction via noninvasive programmed electrical stimulation with the cardioverter and efficacy of cardioversion. Induction and termination of VT were attempted at implantation and approximately every 3 months thereafter. All patients had coronary artery disease and were receiving antiarrhythmic drug therapy (amiodarone in eight). VT cycle length, morphology, and mode of induction were reproducible on multiple occasions in nine patients; clinical VT was induced inconsistently in two patients. Multiple VT episodes in five patients had one morphology, whereas two morphologies occurred in six patients. Synchronization of the shock within the QRS complex and right ventricular effective refractory periods determined via the cardioverter remained constant over the follow-up period. VT was terminated on every occasion in nine patients and on eight of nine occasions in one patient. Tachycardia was accelerated on three of five occasions in one patient. Consistently effective cardioversion energy (0.2 to 2.0 J) increased modestly in four patients. We conclude that patients with inducible monomorphic VT usually have sustained VT with similar characteristics inducible over a period of time and cardioversion and sensing functions of the cardioverter remain relatively stable over time.

Kent bundle interruption for ventricular preexcitation has been successfully accomplished utilizing several different surgical techniques. The external closed-heart technique of Guiraudon combining surgical dissection and cryoablation has been used to interrupt 52 accessory pathways in 47 consecutive patients since May, 1985. The 35 male and 12 female patients ranged in age from 10 to 67 years (mean, 30 years). There were 25 left free wall, 13 right free wall, 13 posterior septal, and 1 anterior septal accessory pathways. Preoperative and intraoperative electrophysiological studies were performed in all patients to induce the arrhythmia and localize all accessory pathways. The operation consisted of dissection of the atrioventricular fat pad. Following this, the delta wave and retrograde accessory pathway conduction disappeared, thereby indicating successful pathway ablation. In 4 patients with right-sided accessory pathways, interruption of the pathway required cryoablation. Cryolesions (made with cryo-probe at −60°C for two minutes) were created in the region of the accessory pathway insertion. All accessory pathways were successfully ablated without any deaths or heart block. Concomitant surgical procedures were performed in 4 patients. Two patients required a second operation the next day for an accessory pathway not found at the initial operation. Three patients had postpericardiotomy syndrome, and 4 had recurrent atrial fibrillation requiring therapy. The remaining patients have had no arrhythmia recurrence and have remained drug free after a follow-up of 1 month to 22 months (mean, 12.5 months). We conclude that the closed-heart technique of accessory pathway ablation is safe and reproducible, obviates the necessity for aortic cross-clamping and cardioplegic arrest, and allows instantaneous monitoring of conduction over the pathway.

We evaluated the effects of amiodarone in 45 patients with recurrent ventricular tachycardia or ventricular fibrillation. At a mean follow-up time of 12.7 +/- 8.8 months (range, three to 36), amiodarone was successful in nine of 16 patients with recurrent ventricular fibrillation and 21 of 29 with recurrent ventricular tachycardia. During amiodarone therapy, ventricular tachycardia could be induced in 18 of 19 patients in whom it had been induced before therapy, but only six of these 19 had spontaneous recurrence during follow-up. Side effects included corneal microdeposits, hyperthyroidism, blue skin, nausea, and symptomatic bradycardia. Pulmonary fibrosis occurred in three patients. Doses of up to 2000 mg a day did not produce cardiac toxicity, but neurologic side effects precluded long-term therapy at this dose. We conclude that amiodarone is effective for long-term therapy of recurrent ventricular tachyarrhythmias, that induction of arrhythmia during therapy does not always predict efficacy, and that side effects are frequent but do not usually limit therapy.

We examined the influence of ventricular tachycardia (VT) cycle length and antiarrhythmic drugs on the frequency of VT termination and acceleration by single and double extrastimuli and right ventricular burst pacing. In 57 patients, 89 episodes of sustained VT (32 control, 57 drug) were induced by programmed electrical stimulation. Overall, 60 of 89 (67%) episodes of ventricular tachycardia were terminated by means of programmed electrical stimulation. In patients with relatively slow ventricular tachycardia (VT cycle length greater than or equal to 350 msec) pacing terminated 37 of 44 (84%) episodes but terminated only 24 of 45 (51%) episodes of more rapid VT (VT cycle length less than or equal to 349 msec, p less than 0.005). Pacing successfully terminated VT in nine of 49 (18%) episodes using a single extrastimulus, 22 of 52 (42%) episodes using double extrastimuli, and 40 of 66 (61%) episodes using burst right ventricular pacing. VT acceleration occurred in none of 49 attempts with a single extrastimulus, in eight of 52 (15%) attempts with double extrastimuli, and in 12 of 66 (18%) attempts using burst right ventricular pacing. During therapy, the frequency of either ventricular tachycardia termination or acceleration did not change regardless of the pacing termination method used. However, by prolonging the mean VT cycle length from 311.1 +/- 82.2 msec to 401.9 +/- 103.5 msec (p less than 0.01), drugs increased the overall frequency of VT termination. We conclude that: (1) pacing terminates VT more frequently if the VT cycle length is long and if right ventricular bursts are used, (2) burst right ventricular pacing increases the risk of VT acceleration, and (3) drugs increase the frequency of ventricular tachycardia termination by prolonging VT cycle length but do not affect frequency of VT acceleration.

Ventricular tachycardia induced by programmed electrical stimulation during amiodarone therapy often does not preclude a good clinical response. The purpose of this study was to determine whether use of discriminant analysis could distinguish patients who remained asymptomatic from those who subsequently developed symptomatic ventricular tachycardia or cardiac arrest. Studies were performed in 37 patients with sustained ventricular tachycardia who still had ventricular tachycardia induced during programmed electrical stimulation during amiodarone therapy. The mean follow-up time was 14.1 ± 1.3 months (± SEM). Twenty-three patients remained asymptomatic, whereas 14 patients had symptomatic recurrence of their ventricular tachycardia.In patients with recurrence of arrhythmia compared with asymptomatic patients, administration of amiodarone caused a longer ventricular effective refractory period (296 ± 8 versus 271 ± 7 ms, p < 0.05) and a greater change in corrected QT [QTc] interval (90 ± 18 versus 44 ± 9 ms, p < 0.02), but no difference in the decrease in premature ventricular complexes after treatment with amiodarone. During amiodarone therapy, nonbundle branch reentrant repetitive ventricular responses were induced by a single ventricular extrastimulus during sinus rhythm in 9 of 14 patients with recurrent arrhythmias compared with 2 of 21 asymptomatic patients (p = 0.001). Also, less aggressive pacing techniques were required to induce ventricular tachycardia in 9 of 14 symptomatic patients compared with 4 of 23 asymptomatic patients (p < 0.02). A discriminant analysis using the presence of nonbundle branch reentrant repetitive ventricular responses, change in method of ventricular tachycardia induction and either the change in QTcinterval or ventricular effective refractory period correctly identified clinical outcome in 90% of the patients, and all patients with recurrent arrhythmias were classified correctly. It is concluded that electrophysiologic testing during amiodarone therapy can provide data that identify patients who appear to be at risk for development of ventricular tachycardia after hospital discharge.

Natural history, structural substrate, electrocardiographic and electrophysiologic characteristics and therapy were evaluated in 18 patients who demonstrated repetitive ventricular tachycardia, defined as repeated episodes of ventricular tachycardia that had a uniform QRS configuration and normal sinus-conducted QRS complexes between the episodes of tachycardia. The patients were young (mean age 37 years) and frequently had a long history of arrhythmias before this evaluation; only two patients has a history of syncope and six were completely asymptomatic. Fourteen patients had no evidence of underlying structural heart disease, three had mitral valve prolapse and one had congestive cardiomyopathy. Episodes of ventricular tachycardia tended to occur in clusters over a 24 hour electrocardiographic recording period. Repetitive ventricular tachycardia was induced in two of nine patients by programmed electrical stimulation, and in seven patients incremental atrial and ventricular pacing suppressed spontaneous arrhythmia. In the one patient whose tachycardia was induced by incremental ventricular pacing there was an inverse relation between pacing cycle length and the interval from the last paced complex to the first complex of ventricular tachycardia, indicating there was overdrive suppression. At a follow-up time of 0.5 to 8 years no patient had died or had worsening of symptoms. Encainide completely eliminated episodes of ventricular tachycardia during acute treatment in five of six patients tested. Seven patients received no antiarrhythmic therapy and the arrhythmia appeared to have spontaneously resolved in four of these patients. Repetitive ventricular tachycardia appears to have distinct clinical and electrophysiologic characteristics. In this series the arrhythmia had a good prognosis and often required no treatment. The electrophysiologic features are consistent with a mechanism of automaticity.

Four patients with ventricular preexcitation whose syncope initially was attributed to an arrhythmia utilizing the accessory pathway are presented. At electrophysiologic study, the electrophysiologic characteristics of the accessory pathways were considered unlikely to support a tachycardia of a rate sufficient to result in syncope. Programmed Stimulation of the right ventricle, however, reproducibly induced ventricular tachycardia to which the syncope was subsequently attributed in 3 patients. The importance of identifying ventricular tachycardia as the cause of syncope in these patients is emphasized.

Cibenzoline, a new antiarrhythmic agent, was tested in 26 patients who had symptomatic ventricular tachycardia (24 patients) or premature ventricular complexes (2 patients) unresponsive to conventional drugs. Cibenzoline was given orally every 8 hours to maximal doses of 65 mg in 2 patients, 81.25 mg in 22 patients and 97.5 mg in 2 patients. Cibenzoline abolished spontaneous episodes of ventricular tachycardia in 8 of 16 patients with ventricular tachycardia during a 72 hour control electrocardiographic recording, and 7 of 22 patients had greater than 83% decrease in premature ventricular complexes compared with control. The PR interval increased 14% (p < 0.001), QRS duration increased 17% (p < 0.001), QT interval did not change and mean ejection fraction in 10 patients did not change.Electrophysiologic studies were performed on 10 patients in the control period and during maximal cibenzoline dosage. Cibenzoline did not affect electrophysiologic properties of the atrium or atrioventricular (AV) node. It prolonged the ventricular effective (223 ± 16 to 241 ± 22 ms, p < 0.02) and functional (247 ± 18 to 264 ± 25 ms, p < 0.02) refractory periods. At control electrophysiologic studies, ventricular tachycardia was induced in 9 of 10 patients (mean cycle length 210 ± 31 ms). Cibenzoline therapy prevented ventricular tachycardia induction in two patients, and in the other seven patients the mean ventricular tachycardia cycle length increased from 210 to 260 ms. The one patient with no ventricular arrhythmia induced during the control study still had no arrhythmia induced while receiving cibenzoline. Among six patients receiving cibenzoline during follow-up, one patient died of recurrent myocardial infarction, two patients stopped taking cibenzoline because of recurrent veutricular tachycardia and three patients have continued taking cibenzoline for 10 ± 4 months with control of symptomatic arrhythmias.Thus, cibenzoliue suppressed ventricular tachycardia and premature veutricular complexes in some patients unresponsive to conventional drugs and was well tolerated. Cibenzoline significantly prolonged ventricular effective and functional refractory periods and had minimal negative hemodynamic effects.

This study examined the usefulness of programmed electrical stimulation in managing 83 patients who had ventricular tachycardia not due to coronary artery disease. Among 39 patients with a history of sustained ventricular tachycardia, programmed stimulation induced ventricular tachycardia in 14 of 14 patients with mitral valve prolapse or primary electrical disease (arrhythmias without evidence of structural heart disease) and in 13 of 25 with cardiomyopathy (total 27 of 39, 69 percent). Programmed stimulation induced nonsustained ventricular tachycardia in 15 (34 percent) of 44 patients with a history of nonsustained tachycardia (5 of 13 with mitral valve prolapse, 6 of 19 with primary electrical disease and 4 of 12 with cardiomyopathy). Seventy-three of the 83 patients were treated with antiarrhythmic drugs and then followed up for 14.4 ± 11.4 months (mean ± standard deviation). Drug therapy was determined with serial electrophysiologic testing in 31 patients. Twenty-four of these 31 patients had a history of sustained ventricular tachycardia, and drugs prevented induction of ventricular tachycardia in 9 (none of whom manifested symptomatic events) but did not prevent it in 15 (6 of whom had symptomatic events). Among seven patients with a history of nonsustained ventricular tachycardia, drugs prevented induction of ventricular tachycardia in five (none of whom had symptomatic events) and did not prevent it in two (none of whom had symptomatic events). Forty-two patients were treated using the results of noninvasive testing. Drugs suppressed spontaneous ventricular tachycardia in 15 of 15 patients with a history of sustained tachycardia (7 of whom had symptomatic events including one sudden death), and in 26 of 27 with a history of nonsustained tachycardia (6 of whom had symptomatic events including one sudden death). Thus, in patients with ventricular tachycardia unrelated to coronary artery disease: (1) programmed electrical stimulation induced ventricular tachycardia less often than in patients whose tachycardia was due to coronary artery disease; (2) programmed stimulation induced ventricular tachycardia less often in patients with a history of nonsustained versus sustained tachycardia; and (3) suppression of inducible ventricular tachycardia appeared to predict effective drug therapy but drug therapy predicted with noninvasive testing appeared to be unreliable.

Antiarrhythmic therapy in 506 consecutive patients undergoing 1,268 antiarrhythmic drug trials for ventricular tachycardia or ventricular fibrillation was reviewed for evidence of arrhythmogenic drug effect defined as the occurrence of a new form of ventricular tachyarrhythmia temporally associated with initiation of drug therapy or dosage increase. Arrhythmogenic effects occurred in 6.9% of patients and 3.4% of drug trials. This ranged from a high of 11.8% caused by encainide to none occurring with procainamide, tocainide or beta-adrenergic blocking drugs. The incidence of arrhythmogenesis was significantly greater in patients whose presenting arrhythmia was sustained ventricular tachycardia than it was in those who presented with nonsustained ventricular tachycardia or ventricular fibrillation (p = 0.02). Decreased systolic function measured echocardiographically at the base of the left ventricle was associated with an increased incidence of arrhythmogenic effects (p = 0.006) whereas global left ventricular ejection fraction was not. Age, gender, cardiac diagnosis, location of prior myocardial infarction and New York Heart Association functional class for heart failure were not related to the occurrence of drug-induced arrhythmias. These findings emphasize the need for in-hospital cardiac monitoring during initiation of antiarrhythmic drug therapy for ventricular tachyarrhythmias.

The development of the transvenous cardioverter, from the initial animal studies, to the clinical studies using temporary leads, to the initial permanent implants is described. Shocks less than or equal to 2.0 joules synchronized to the QRS complex and delivered through a specially designed catheter electrode placed in the apex of the right ventricle successfully terminate most episodes of ventricular tachycardia in patients. The implanted unit which also serves as a demand ventricular pacemaker, can be used to perform programmed electrophysiologic studies. Future devices must be capable of defibrillation and more accurate arrhythmia detection.

We assessed the value of clinical electrophysiologic study using intracardiac recording and programed electrical stimulation in 34 patients who had unexplained syncope and/or presyncope. All patients had normal electrocardiograms, and no abnormality was detected by clinical examination, ambulatory electrocardiographic recording, or treadmill testing. The electrophysiologic results were diagnostic in four patients (11.8 percent) and led to appropriate therapy that totally relieved symptoms. The results were abnormal but not diagnostic in two patients (5.8 percent) and normal in the remaining 28 patients (82.4 percent). The patients were followed for a mean period of 15 months (range two to 44) after electrophysiologic testing. Sixteen patients (47 percent) had no further episodes in the absence of any intervention. In four patients (11.8 percent), a definitive diagnosis was made during follow-up. In seven patients, permanent pacing was instituted empirically with relief of syncope. Two patients continued to have syncopal spells. We conclude that the diagnostic yield of electrophysiologic testing is low in a patient population that has no electrocardiographic abnormality or clinical evidence of cardiac disease. Empirical permanent pacing in patients with symptoms continuing after our study appeared to be beneficial, but this result is difficult to evaluate because of the high incidence of spontaneous remission in this group. Persistent attempts to document electrocardiographic abnormalities during a typical episode of symptoms appears to be the only definitive way to confirm or exclude an arrhythmic cause of the symptoms.

Induction of ventricular tachycardia (VT) at electrophysiologic study in patients taking amiodarone poorly predicts recurrence of VT. Consequently, a discriminant function was developed (using parameters based on retrospective data) that appeared to identify high-risk patients. These parameters included ventricular effective refractory period, corrected QT interval, initiation of a repetitive ventricular response and the mode of VT induction. In the present study these parameters were prospectively evaluated in 60 patients with coronary artery disease and sustained VT or ventricular fibrillation (VF), in whom VT was still induced at electrophysiologic study during amiodarone therapy. Thirteen patients had recurrent events (sudden death in 8 and sustained VT in 5) and 47 patients had no symptomatic arrhythmia recurrence (follow-up for 16 +/- 2 months, mean +/- standard error of the mean). The ventricular effective refractory period, corrected QT interval and presence of a repetitive ventricular response did not discriminate between patients with and without symptomatic arrhythmia recurrence. However, an easier mode of VT induction during amiodarone therapy versus control was highly predictive of arrhythmia recurrence: 9 of 13 (69%) recurrences were in this group. In contrast, only 4 of 44 (9%) patients who had either the same or harder mode of VT induction had a recurrent event. Overall, 9 of 16 (56%) patients with an easier mode of VT induction had a recurrence, including 6 of the 8 patients with subsequent sudden cardiac death. It is concluded that electrophysiologic testing during amiodarone therapy is useful to identify high-risk patients.

Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine- 123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction.Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake.This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

Programmed ventricular stimulation, electrophysiologic effects of various antiarrhythmic drugs, and the results of serial electrophysiologic testing in patients with ventricular arrhythmias are discussed. The use of discriminant analysis to predict the efficacy of antiarrhythmic drugs is also briefly analyzed.

re-entry andbundle-branch re-entry in47patients withand in50patients without ventricular tachycardia. We alsocompared theprevalence ofrepetitive ventricular responsesusing twotypesofelectrophysiological stimulation: single prematureventricular stimulation during sinus rhythm oratrial pacing, andsingle prematureventricular stimulation during ventricular pacing.Inpatients whohadventricular tachycardia, prematureventricular stimulation during ventricular pacing induced non-bundle-branch re-entry more often thanduring atrial pacing (70-2% versus333%).Bothmethods ofstimulation induced non-bundle-branch re-entry more often inpatients whohadventricular tachycardia thaninthose whodidnot.Inbothgroupsof patients, bundle-branch re-entry was rareduring atrial pacing andmore common butequally prevalent during ventricular pacing. Todetermine ifinduced non-bundle-branch re-entry could identify patients atrisk ofdeveloping future symptomatic ventricular tachycardia or sudden death, 59patients whohada history of documented ventricular tachycardia hadanelectrophysiological study just before discharge andwere followed for anaverageof109months. Non-bundle-branch re-entry induced during ventricular and atrial pacing hadapredictive accuracyof59%and64%,respectively. Thepredictive accuracyof non-bundle-branch re-entry induced during atrial pacing appeared tobegreaterinpatients whoalso hadventricular tachycardia induced during the sameelectrophysiology

The effects of amiodarone on the pharmacokinetic and electrophysiologic properties of procainamide were examined in eight patients treated for recurrent ventricular arrhythmias who received intravenous procainamide, 6 to 15 mg/kg, at control and after 1 to 2 weeks of oral amiodarone treatment. Compared with control, procainamide plasma clearance decreased from 0.43 +/- 0.12 L/kg-hr to 0.33 +/- 0.12 L/kg-hr (P less than 0.01), plasma elimination half-life increased from 3.77 +/- 0.64 hours to 5.21 +/- 0.42 hours (P less than 0.01), and volume of distribution was unchanged from 2.31 +/- 0.74 L/kg to 2.47 +/- 0.90 L/kg during amiodarone treatment. As single agents, intravenous procainamide and oral amiodarone produced equivalent increases in QRS duration, rate-corrected QT interval, right ventricular effective refractory period, and cycle length of induced ventricular tachycardia. After the addition of intravenous procainamide to amiodarone the QRS duration, rate-corrected QT interval, and, in six of eight patients, ventricular tachycardia cycle length were significantly increased compared with control or either drug alone, suggesting additive electrophysiologic effect. However, acceleration of induced ventricular tachycardia occurred in one patient with combined treatment, suggesting a potential for adverse electrophysiologic interactions. These findings indicate that amiodarone has pharmacokinetic and electrophysiologic interactions with procainamide and suggest that the intravenous dose of procainamide be reduced by 20% to 30% during concurrent drug administration.

Twenty-six patients had ventricular tachycardia initiated at control electrophysiologic study and had a repeat study during oral propafenone therapy. Ten patients had had sustained ventricular tachycardia, 6 cardiac arrest and 10 symptomatic, nonsustained ventricular tachycardia. Twenty-two patients had heart disease, 18 of whom had coronary artery disease. During propafenone therapy, ventricular tachycardia could not be initiated during programmed ventricular stimulation in 5 patients, and in 21 patients the cycle length of induced ventricular tachycardia increased from 246 +/- 42 ms at control to 355 +/- 96 ms (p less than 0.001). Seventeen patients were discharged with propafenone therapy and have been followed for a mean of 11 months. No symptomatic ventricular tachycardia recurred in the 5 patients without inducible ventricular tachycardia during drug treatment. Six of 12 patients with inducible ventricular tachycardia during the drug study have remained asymptomatic. In conclusion, propafenone substantially prolongs the cycle length of ventricular tachycardia, and initiation of ventricular tachycardia by programmed ventricular stimulation at drug study does not preclude a favorable clinical outcome.

We have endeavored to relate known electrophysiologic mechanisms of arrhythmia development to clinically occurring arrhythmias, realizing that definitive conclusions can only be surmised at present. Arrhythmias that may be due to disorders of impulse formation include slow atrial, junctional, and ventricular escape rhythms, certain types of atrial tachycardias (such as those produced by digitalis), accelerated junctional (nonparoxysmal junctional tachycardia) and idioventricular rhythms, and parasystole. Arrhythmias that may be due to disorders of impulse conduction include flutter and fibrillation, atrioventricular nodal reentrant tachycardia, reciprocating tachycardias associated with an accessory pathway, sinus nodal reentry, some atrial tachycardias, and many ventricular tachycardias. Understanding the mechanism of the tachycardia, in some instances, helps direct rational therapeutic approaches.

We examined the long-term effects of closed instrumental mitral commissurotomy on mitral valve area (MVA) in 18 patients, followed for as long as 14 years after successful operation. Each patient had preoperative and early postoperative cardiac catheterization; late postoperative determination of MVA was obtained 10-14 years (mean 12.2 years) after commissurotomy. In 17 patients, the MVA was determined by cross-sectional echocardiography and in one patient by repeat cardiac catheterization. Thirteen of 18 patients had no change in MVA between early postoperative study (mean MVA = 2.7 cm2) and late postoperative study (mean MVA = 2.9 CM2). MVA in five patients decreased 0.7-2.2 cm2 (mean 1.4 cm2) during the follow-up period. In these five patients, the mean MVA at early postoperative study was 2.7 cm2 and at late postoperative study was 1.3 cm2 (p less than 0.001). At late postoperative evaluation, cardiac symptoms were associated with severity of mitral stenosis but did not predict restenosis. A successful, closed, instrumental mitral commisurotomy can provide substantial long-term improvement in MVA.

Amiodarone has been used in the therapy of supraventricular and ventricular tachycardia, and has often been categorised as a class III rather than a class I agent. However, in patients with ventricular arrhythmias, amiodarone 800mg daily for 14 days prolonged the right ventricular effective refractory period by a mean of 18.8 msec (p less than 0.05), and HV interval by a mean of 5.2 msec (p less than 0.05), these changes being similar to those noted with drugs such as quinidine, procainamide, disopyramide and encainide. The antiarrhythmic efficacy of amiodarone was evaluated in 196 patients with recurrent sustained ventricular tachycardia, recurrent ventricular fibrillation or recurrent nonsustained ventricular tachycardia. Coronary artery disease, dilated (congestive) cardiomyopathy, or other forms of heart disease were present in most patients. After 1 month of therapy, 177 patients continued to receive amiodarone and, during the remainder of the follow-up period, 139 patients had no recurrence of spontaneous ventricular tachycardia or ventricular fibrillation. Sudden cardiac death occurred in 15 patients after a mean treatment period of 10.4 months. Overall, amiodarone was an effective form of therapy in patients with ventricular tachycardia and ventricular fibrillation.