Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era.

BACKGROUND: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. METHODS: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. monotherapy versus combination therapy). RESULTS: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). CONCLUSIONS: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

Renal function and the long-term clinical outcomes of cardiac resynchronization therapy with or without defibrillation.

BACKGROUND AND AIMS: Patients with moderate-to-severe chronic kidney disease (CKD) are underrepresented in clinical trials of cardiac resynchronization therapy (CRT)-defibrillation (CRT-D) or CRT-pacing (CRT-P). We sought to determine whether outcomes after CRT-D are better than after CRT-P over a wide spectrum of CKD. METHODS AND RESULTS: Clinical events were quantified in relation to preimplant estimated glomerular filtration rate (eGFR) after CRT-D (n = 410 [39.2%]) or CRT-P (n = 636 [60.8%]) implantation. Over a follow-up period of 3.7 years (median, interquartile range: 2.1-5.7), the eGFR < 60 group (n = 598) had a higher risk of total mortality (adjusted hazard ratio [aHR]: 1.28; P = 0.017), total mortality or heart failure (HF) hospitalization (aHR: 1.32; P = 0.004), total mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.34; P = 0.002), and cardiac mortality (aHR: 1.33; P = 0.036), compared to the eGFR ≥ 60 group (n = 448), after covariate adjustment. In analyses of CRT-D versus CRT-P, CRT-D was associated with a lower risk of total mortality (eGFR ≥ 60 HR: 0.65; P = 0.028; eGFR < 60 HR: 0.64, P = 0.002), total mortality or HF hospitalization (eGFR ≥ 60 aHR: 0.66; P = 0.021; eGFR < 60 aHR: 0.69, P = 0.007), total mortality or hospitalization for MACEs (eGFR ≥ 60 aHR: 0.70; P = 0.039; eGFR < 60 aHR: 0.69, P = 0.005), and cardiac mortality (eGFR ≥ 60 aHR: 0.60; P = 0.026; eGFR < 60 aHR: 0.55; P = 0.003). CONCLUSION: In CRT recipients, moderate CKD is associated with a higher mortality and morbidity compared to normal renal function or mild CKD. Despite less favorable absolute outcomes, patients with moderate CKD had better outcomes after CRT-D than after CRT-P.

Long-term clinical outcomes of cardiac resynchronization therapy with or without defibrillation: impact of the aetiology of cardiomyopathy.

Aims: There is a continuing debate as to whether cardiac resynchronization therapy-defibrillation (CRT-D) is superior to CRT-pacing (CRT-P), particularly in patients with non-ischaemic cardiomyopathy (NICM). We sought to quantify the clinical outcomes after primary prevention of CRT-D and CRT-P and identify whether these differed according to the aetiology of cardiomyopathy. Methods and results: Analyses were undertaken in the total study population of patients treated with CRT-D (n = 551) or CRT-P (n = 999) and in propensity-matched samples. Device choice was governed by the clinical guidelines in the United Kingdom. In univariable analyses of the total study population, for a maximum follow-up of 16 years (median 4.7 years, interquartile range 2.4-7.1), CRT-D was associated with a lower total mortality [hazard ratio (HR) 0.72] and the composite endpoints of total mortality or heart failure (HF) hospitalization (HR 0.72) and total mortality or hospitalization for major adverse cardiac events (MACE; HR 0.71) (all P < 0.001). After propensity matching (n = 796), CRT-D was associated with a lower total mortality (HR 0.72) and the composite endpoints (all P < 0.01). When further stratified according to aetiology, CRT-D was associated with a lower total mortality (HR 0.62), total mortality or HF hospitalization (HR 0.63), and total mortality or hospitalization for MACE (HR 0.59) (all P < 0.001) in patients with ischaemic cardiomyopathy (ICM). There were no differences in outcomes between CRT-D and CRT-P in patients with NICM. Conclusion: In this study of real-world clinical practice, CRT-D was superior to CRT-P with respect to total mortality and composite endpoints, independent of known confounders. The benefit of CRT-D was evident in ICM but not in NICM.

Mechanical effects of left ventricular midwall fibrosis in non-ischemic cardiomyopathy.

BACKGROUND: Left ventricular (LV) mid-wall fibrosis (MWF), which occurs in about a quarter of patients with non-ischemic cardiomyopathy (NICM), is associated with high risk of pump failure. The mid LV wall is the site of circumferential myocardial fibers. We sought to determine the effect of MWF on LV myocardial mechanics. METHODS: Patients with NICM (n = 116; age: 62.8 ± 13.2 years; 67% male) underwent late gadolinium enhancement cardiovascular magnetic resonance (CMR) and were categorized according to the presence (+) or absence (-) of MWF. Feature tracking (FT) CMR was used to assess myocardial deformation. RESULTS: Despite a similar LVEF (24.3 vs. 27.5%, p = 0.20), patients with MWF (32 [24%]) had lower global circumferential strain (Ɛcc: -6.6% vs. -9.4 %, P = 0.004), but similar longitudinal (Ɛll: -7.6 % vs. -9.4 %, p = 0.053) and radial (Ɛrr: 14.6% vs. 17.8% p = 0.18) strain. Compared with - MWF, + MWF was associated with reduced LV systolic, circumferential strain rate (-0.38 ± 0.1 vs. -0.56 ± 0.3 s(-1), p = 0.005) and peak LV twist (4.65 vs. 6.31°, p = 0.004), as well as rigid LV body rotation (64 % vs. 28 %, P <0.001). In addition, +MWF was associated with reduced LV diastolic strain rates (DSRcc: 0.34 vs. 0.46 s(-1); DSRll: 0.38 vs. 0.50s(-1); DSRrr: -0.55 vs. -0.75 s(-1); all p <0.05). CONCLUSIONS: MWF is associated with reduced LV global circumferential strain, strain rate and torsion. In addition, MWF is associated with rigid LV body rotation and reduced diastolic strain rates. These systolic and diastolic disturbances may be related to the increased risk of pump failure observed in patients with NICM and MWF.

The clinical outcome of cardiac resynchronization therapy in post-surgical valvular cardiomyopathy.

AIMS: Trials have shown that cardiac resynchronization therapy (CRT) is effective in patients with 'non-ischaemic cardiomyopathy'. Patients with post-surgical valvular cardiomyopathy (PSVCM) have been excluded from such trials. We sought to compare the clinical outcome of CRT in patients with PSVCM, idiopathic dilated cardiomyopathy (IDCM), or ischaemic cardiomyopathy (ICM). METHODS AND RESULTS: Clinical events and response to CRT were quantified in 556 patients (PSVCM = 38; IDCM = 165; ICM = 353) over 4.52 years [median, inter-quartile range (IQR): 4.42]. Response to CRT was defined as survival for ≥1 year free of hospitalizations plus improvement by ≥1 NYHA class or ≥25% in 6-min walking distance. Cardiac resynchronization therapy was initiated at 5.86 years (median, IQR: 9.86) after aortic valve replacement (73.7%) or mitral valve replacement/repair (44.7%). Compared with PSVCM, IDCM was associated with a lower total mortality [hazards ratio, HR: 0.54 (95% confidence interval, CI 0.34-0.84)], cardiac mortality [HR: 0.43 (95% CI 0.26-0.70)], and total mortality or major adverse cardiovascular events [HR: 0.57 (95% CI 0.37-0.87)], independent of known confounders. Compared with PSVCM, ICM was associated with a similar risk of death from pump failure [HR: 0.83 (95% CI 0.50-1.37)] and IDCM was associated with a lower risk [HR: 0.46 (95% CI 0.26-0.82)]. Response to CRT was similar across the groups. CONCLUSIONS: Compared with IDCM, PSVCM was associated with a worse outcome after CRT. Outcomes from PSVCM were similar to ICM. These findings indicate that PSVCM behaves very differently to IDCM after CRT.

Haemodynamic effects of cardiac resynchronization therapy using single-vein, three-pole, multipoint left ventricular pacing in patients with ischaemic cardiomyopathy and a left ventricular free wall scar: the MAESTRO study.

AIMS: The clinical response to cardiac resynchronization therapy (CRT) is variable. Multipoint left ventricular (LV) pacing could achieve more effective haemodynamic response than single-point LV pacing. Deployment of an LV lead over myocardial scar is associated with a poor haemodynamic response to and clinical outcome of CRT. We sought to determine whether the acute haemodynamic response to CRT using three-pole LV multipoint pacing (CRT3P-MPP) is superior to that to conventional CRT using single-site LV pacing (CRTSP) in patients with ischaemic cardiomyopathy and an LV free wall scar. METHODS AND RESULTS: Sixteen patients with ischaemic cardiomyopathy [aged 72.6 ± 7.7 years (mean ± SD), 81.3% male, QRS: 146.0 ± 14.2 ms, LBBB in 14 (87.5%)] in whom the LV lead was intentionally deployed straddling an LV free wall scar (assessed using cardiac magnetic resonance), underwent assessment of LV + dP/dtmax during CRT3P-MPP and CRTSP. Interindividually, the ΔLV + dP/dtmax in relation to AAI pacing with CRT3P-MPP (6.2 ± 13.3%) was higher than with basal and mid CRTSP (both P < 0.001), but similar to apical CRTSP. Intraindividually, significant differences in the ΔLV + dP/dtmax to optimal and worst pacing configurations were observed in 10 (62.5%) patients. Of the 8 patients who responded to at least one configuration, CRT3P-MPP was optimal in 5 (62.5%) and apical CRTSP was optimal in 3 (37.5%) (P = 0.0047). CONCLUSIONS: In terms of acute haemodynamic response, CRT3P-MPP was comparable an apical CRTSP and superior to basal and distal CRTSP. In the absence of within-device haemodynamic optimization, CRT3P-MPP may offer a haemodynamic advantage over a fixed CRTSP configuration.

Comparison of magnetic resonance feature tracking for systolic and diastolic strain and strain rate calculation with spatial modulation of magnetization imaging analysis.

PURPOSE: To compare cardiovascular magnetic resonance-feature tracking (CMR-FT) with spatial modulation of magnetization (SPAMM) tagged imaging for the calculation of short and long axis Lagrangian strain measures in systole and diastole. MATERIALS AND METHODS: Healthy controls (n = 35) and patients with dilated cardiomyopathy (n = 10) were identified prospectively and underwent steady-state free precession (SSFP) cine imaging and SPAMM imaging using a gradient-echo sequence. A timed offline analysis of images acquired at identical horizontal long and short axis slice positions was performed using CMR-FT and dynamic tissue-tagging (CIMTag2D). Agreement between strain and strain rate (SR) values calculated using these two different methods was assessed using the Bland-Altman technique. RESULTS: Across all participants, there was good agreement between CMR-FT and CIMTag for calculation of peak systolic global circumferential strain (-22.7 ± 6.2% vs. -22.5 ± 6.9%, bias 0.2 ± 4.0%) and SR (-1.35 ± 0.42 1/s vs. -1.22 ± 0.42 1/s, bias 0.13 ± 0.33 1/s) and early diastolic global circumferential SR (1.21 ± 0.44 1/s vs. 1.07 ± 0.30 1/s, bias -0.14 ± 0.34 1/s) at the subendocardium. There was satisfactory agreement for derivation of peak systolic global longitudinal strain (-18.1 ± 5.0% vs. -16.7 ± 4.8%, bias 1.3 ± 3.8%) and SR (-1.04 ± 0.29 1/s vs. -0.95 ± 0.32 1/s, bias 0.09 ± 0.26 1/s). The weakest agreement was for early diastolic global longitudinal SR (1.10 ± 0.40 1/s vs. 0.67 ± 0.32 1/s, bias -0.42 ± 0.40 1/s), although the correlation remained significant (r = 0.42, P < 0.01). CMR-FT generated these data over four times quicker than CIMTag. CONCLUSION: There is sufficient agreement between systolic and diastolic strain measures calculated using CMR-FT and myocardial tagging for CMR-FT to be considered as a potentially feasible and rapid alternative.

Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation.

BACKGROUND: Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias. OBJECTIVES: The purpose of this study was to determine whether presence of myocardial fibrosis on visual assessment (MFVA) and gray zone fibrosis (GZF) mass predicts sudden cardiac death (SCD) and ventricular fibrillation/sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation. METHODS: In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of SCD and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation. RESULTS: Among 700 patients (age 68.0 ± 12.0 years), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over median 6.93 years (IQR: 5.82-9.32 years). MFVA predicted SCD (HR: 26.3; 95% CI: 3.7-3,337; negative predictive value: 100%). In competing risk analyses, MFVA also predicted the arrhythmic endpoint (subdistribution HR: 19.9; 95% CI: 6.4-61.9; negative predictive value: 98.6%). Compared with no MFVA, a GZF mass measured with the 5SD method (GZF5SD) >17 g was associated with highest risk of SCD (HR: 44.6; 95% CI: 6.12-5,685) and the arrhythmic endpoint (subdistribution HR: 30.3; 95% CI: 9.6-95.8). Adding GZF5SD mass to MFVA led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint. CONCLUSIONS: In CIED recipients, MFVA excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF5SD mass added predictive value in relation to SCD and the arrhythmic endpoint.

Low-Density Lipoprotein Cholesterol Level Trends and the Development of Cardiac Allograft Vasculopathy After Heart Transplantation.

BACKGROUND: Unlike the relationship with atherosclerotic coronary artery disease, that between low-density lipoprotein cholesterol (LDL-C) and cardiac allograft vasculopathy (CAV) is unclear. Our objectives were to characterize lipid profiles early after heart transplantation (HT) and evaluate the relationship between early LDL-C and the development of CAV. METHODS: We retrospectively reviewed consecutive adults who underwent HT at 2 centres during the time period 2010-2018. The primary outcome was the incidence of angiographic CAV. The relationship between LDL-C and CAV was assessed using Cox proportional hazards and logistic regression models adjusted a priori for clinically important covariates, including recipient and donor age, recipient sex, ischemic time, and pre-HT diabetes. RESULTS: A total of 386 patients followed for a median (range) of 4.4 (2.8-6.8) years were included. LDL-C at baseline (2.11 ± 0.86 mmol/L) and 1 year after HT (2.20 ± 0.88 mmol/L) was similar (P = 0.21), but it was lower at the end of follow-up (1.89 ± 0.74 mmol/L, P < 0.01). Of 309 patients who underwent angiography, 54% had CAV. The risk of CAV did not vary according to baseline, 1-year, or change from baseline to 1-year LDL-C. The odds of CAV at 1 year were equally likely across LDL-C values (adjusted odds ratio 1.00, 95% confidence interval: 0.61-1.63 for baseline, and adjusted odds ratio 1.25, 95% confidence interval: 0.74-2.10 for 1-year LDL-C). CONCLUSIONS: No association was identified between early LDL-C and the development of CAV. Our findings do not support targeting a specific LDL-C for patients who do not otherwise meet criteria for guideline-recommended LDL-C target levels. Randomized studies are warranted to determine if lipid-lowering to a specific LDL-C target level modifies the risk of CAV.

INTRODUCTION: Contrairement à la relation avec l'athérosclérose coronarienne, la relation entre les concentrations de cholestérol de lipoprotéines à faible densité (cholestérol LDL) et la vasculopathie d'allogreffe cardiaque (VAC) n'est pas claire. Nos objectifs étaient de caractériser les profils lipidiques rapidement après la transplantation cardiaque (TC) et d'évaluer la relation entre les concentrations initiales de cholestérol LDL et l'apparition de la VAC. MÉTHODES: Nous avons passé en revue de façon rétrospective les adultes consécutifs qui avaient subi une TC dans deux établissements durant la période 2010-2018. Le critère d'évaluation principal était la fréquence de la VAC à l'angiographie. Nous avons évalué la relation entre les concentrations de cholestérol LDL et la VAC à l'aide des modèles à risques proportionnels de Cox et de régression logistique ajustés a priori sur les covariables importantes sur le plan clinique, notamment l'âge du receveur et du donneur, le sexe du receveur, la durée de l'ischémie et le diabète pré-TC. RÉSULTATS: Nous avons inclus un total de 386 patients suivis durant une médiane (étendue) de 4,4 (2,8-6,8) ans. Les concentrations initiales de cholestérol LDL (2,11 ± 0,86 mmol/l) et après 1 an (2,20 ± 0,88 mmol/l) étaient similaires (P = 0,21), mais elles étaient plus faibles à la fin du suivi (1,89 ± 0,74 mmol/l, P < 0,01). Parmi les 309 patients qui avaient subi une angiographie, 54 % avaient une VAC. Le risque de VAC ne variait pas en fonction des concentrations de cholestérol LDL du début, après un an, ou ne changeait pas entre le début et après un an. Les cotes de la VAC après 1 an étaient équiprobables dans toutes les valeurs de cholestérol LDL (rapport de cotes ajusté 1,00, intervalle de confiance [IC] à 95 % : 0,61-1,63 au début, et rapport de cotes ajusté 1,25, IC à 95 % : 0,74-2,10 pour les concentrations de cholestérol LDL après un an). CONCLUSIONS: Aucune association n'a été établie entre les concentrations initiales de cholestérol LDL et l'apparition de la VAC. Nos résultats n'étayent pas le ciblage de concentrations particulières de cholestérol LDL chez les patients qui ne satisfaisaient par ailleurs pas aux critères des concentrations cibles de cholestérol LDL recommandées par les lignes directrices. Des études à répartition aléatoire sont justifiées pour déterminer si la diminution des lipides à des concentrations cibles particulières de cholestérol LDL modifie le risque de VAC.

Effect of QRS area reduction and myocardial scar on the hemodynamic response to cardiac resynchronization therapy.

BACKGROUND: Vectorcardiographic QRS area (QRSarea) predicts clinical outcomes after cardiac resynchronization therapy (CRT). Myocardial scar adversely affects clinical outcomes after CRT. OBJECTIVE: The purpose of this study in patients with an ideally deployed quadripolar left ventricular (LV) lead (QUAD) was to determine whether reducing QRSarea leads to an acute hemodynamic response (AHR) and whether scar affects this interaction. METHODS: Patients (n = 26; age 69.2 ± 9.12 years [mean ± SD]) underwent assessment of the maximum rate of change of LV pressure (ΔLV dP/dtmax) during CRT using various left ventricular pacing locations (LVPLs). Cardiac magnetic resonance (CMR) scan was used to localize LV myocardial scar. RESULTS: Interindividually, ΔQRSarea (area under the receiver operating characteristic curve [AUC] 0.81; P <.001) and change in QRS duration (ΔQRSd) (AUC 0.76; P <.001) predicted ΔLV dP/dtmax after CRT. Scar burden correlated with ΔQRSarea (r = 0.35; P = .003), ΔQRSarea (r = 0.35; P = .003), and ΔQRSd (r = 0.46; P <.001). A reduction in QRSarea was observed with LVPLs remote from scar (-3.28 ± 38.1 µVs) or in LVPLs in patients with no scar at all (-43.8 ± 36.8 µVs), whereas LVPLs over scar increased QRSarea (22.2 ± 58.4 µVs) (P <.001 for all comparisons). LVPLs within 1 scarred LV segment were associated with lower ΔLV dP/dtmax (-2.21% ± 11.5%) than LVPLs remote from scar (5.23% ± 10.3%; P <.001) or LVPLs in patients with no scar at all (10.2% ± 7.75%) (both P <.001). CONCLUSION: Reducing QRSarea improves the AHR to CRT. Myocardial scar adversely affects ΔQRSarea and the AHR. These findings may support the use of ΔQRSarea and CMR in optimizing CRT using QUAD.

A hundred heart failure deaths: lessons learnt from the Dr Foster heart failure hospital mortality alert.

Background: Despite advances in evidence-based pharmacotherapy, the latest National Heart Failure Audit (NHFA) has shown that in-hospital mortality of heart failure (HF) remains high with large interhospital variations. University Hospitals Coventry & Warwickshire, a tertiary cardiac centre, received a mortality alert of excess HF deaths based on a high Dr Foster hospital standardised mortality ratio (HSMR). This conflicted with our local NHFA data which showed lower than national average mortality rates. Objective: To review various systemic and individual processes of care in patients admitted with HF and examine the validity of HSMR in HF. Design setting patients: A retrospective case note analysis was performed on a random sample of 100 HF deaths identified by Dr Foster from 2010 to 2016. Measures: Case record reviews were performed on the following aspects of care: admission to appropriate wards, resuscitation status, palliative care input and National Confidential Enquiry into Patient Outcome and Death classification. Primary diagnosis coding, diagnostic accuracy and actual causes of death were examined to assess limitations of HSMR. Results: Despite evidence of lower mortality on cardiology wards, only 28% of patients with acute HF were admitted to a cardiology-ward. Sixty four per cent were considered palliative but only 4.6% were referred to palliative care. The Do Not Attempt Resuscitation order was appropriate in 91% patients but only 74% had this in place. The primary diagnosis of HF was incorrectly coded in 34% while three cases were misdiagnosed. Conclusion: HF may be coded as a cause of death in some cases where the cause is uncertain and misdiagnosed. Although HSMR has many limitations, it is a smoke alarm that should not be ignored.

Long-term follow-up of normal and structural heart ventricular tachycardia catheter ablation: real-world experience from a UK tertiary centre.

Background: Ventricular tachycardia (VT) is associated with increased morbidity and mortality. There is growing evidence for the effectiveness of catheter ablation in improving outcomes in patients with recurrent VT. Consequently the threshold for referral for VT ablation has fallen over recent years, resulting in increased number of procedures. Objective: To evaluate the effectiveness and safety of VT ablation in a real-world tertiary centre setting. Methods: This is a prospective analysis of all VT ablation cases performed at University Hospital Coventry. Follow-up data were obtained from review of electronic medical records and patient interview. The primary endpoint for normal heart VT was death, cardiovascular hospitalisation and VT recurrence, and for structural heart VT was arrhythmic death, VT storm (>3 episodes within 24 hours) or appropriate shock. Results: Forty-seven patients underwent 53 procedures from January 2012 to January 2018. The mean age ±SD was 57±15 years, 68% were male, 81% were Caucasian and 66% were elective cases. The aetiology of VT included normal heart (49%), ischaemic cardiomyopathy (ICM, 36%), dilated cardiomyopathy (9%), hypertrophic cardiomyopathy (4%) and valvular heart disease (2%). Procedural success occurred in 83%, with six major complications. After a median follow-up of 231 days (lower quartile 133, upper quartile 631), the primary outcome occurred in 28% of patients. There were two non-arrhythmic deaths (4%). At a median follow-up of 193 days (129-468), the primary outcome occurred in 19% of patients with ICM, while VT storm/appropriate shocks occurred in three patients (17%). Conclusions: Our real-world registry confirms that VT ablation is safe, and is associated with high acute procedural success and long-term outcomes comparable with randomised controlled studies.

Long-Term Outcomes of Cardiac Resynchronization Therapy Using Apical Versus Nonapical Left Ventricular Pacing.

Background Experimental evidence indicates that left ventricular ( LV ) apical pacing is hemodynamically superior to nonapical LV pacing. Some studies have shown that an LV apical lead position is unfavorable in cardiac resynchronization therapy. We sought to determine whether an apical LV lead position influences cardiac mortality after cardiac resynchronization therapy. Methods and Results In this retrospective observational study, the primary end point of cardiac mortality was assessed in relation to longitudinal (basal, midventricular, or apical) and circumferential (anterior, lateral, or posterior) LV lead positions, as well as right ventricular (apical or septal), assigned using fluoroscopy. Lead positions were assessed in 1189 patients undergoing cardiac resynchronization therapy implantation over 15 years. After a median follow-up of 6.0 years (interquartile range: 4.4-7.7 years), an apical LV lead position was associated with lower cardiac mortality than a nonapical position (adjusted hazard ratio: 0.74; 95% confidence interval, 0.56-0.99) after covariate adjustment. There were no differences in total mortality or heart failure hospitalization. Death from pump failure was lower with apical than nonapical positions (adjusted hazard ratio: 0.69; 95% confidence interval, 0.51-0.94). Compared with a basal position, an apical LV position was also associated with lower risk of sudden cardiac death (adjusted hazard ratio: 0.34; 95% confidence interval, 0.13-0.93). No differences emerged between circumferential LV lead positions or right ventricular positions with respect to any end point. Conclusions In recipients of cardiac resynchronization therapy, an apical LV lead position was associated with better long-term cardiac survival than a nonapical position. This effect was due to a lower risk of pump failure and sudden cardiac death.

Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Recent studies have cast doubt on the benefit of cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) versus pacing (CRT-P) for patients with nonischemic cardiomyopathy (NICM). Left ventricular myocardial scar portends poor clinical outcomes. OBJECTIVES: The aim of this study was to determine whether CRT-D is superior to CRT-P in patients with NICM either with (+) or without (-) left ventricular midwall fibrosis (MWF), detected by cardiac magnetic resonance. METHODS: Clinical events were quantified in patients with NICM who were +MWF (n = 68) or -MWF (n = 184) who underwent cardiac magnetic resonance prior to CRT device implantation. RESULTS: In the total study population, +MWF emerged as an independent predictor of total mortality (adjusted hazard ratio [aHR]: 2.31; 95% confidence interval [CI]: 1.45 to 3.68), total mortality or heart failure hospitalization (aHR: 2.02; 95% CI: 1.32 to 3.09), total mortality or hospitalization for major adverse cardiac events (aHR: 2.02; 95% CI: 1.32 to 3.07), death from pump failure (aHR: 1.95; 95% CI: 1.11 to 3.41), and sudden cardiac death (aHR: 3.75; 95% CI: 1.26 to 11.2) over a maximum follow-up period of 14 years (median 3.8 years [interquartile range: 2.0 to 6.1 years] for +MWF and 4.6 years [interquartile range: 2.4 to 8.3 years] for -MWF). In separate analyses of +MWF and -MWF, total mortality (aHR: 0.23; 95% CI: 0.07 to 0.75), total mortality or heart failure hospitalization (aHR: 0.32; 95% CI: 0.12 to 0.82), and total mortality or hospitalization for major adverse cardiac events (aHR: 0.30; 95% CI: 0.12 to 0.78) were lower after CRT-D than after CRT-P in +MWF but not in -MWF. CONCLUSIONS: In patients with NICM, CRT-D was superior to CRT-P in +MWF but not -MWF. These findings have implications for the choice of device therapy in patients with NICM.

Skeletal muscles, heart, and lung are the main sources of oxygen radicals in old rats.

The aim of this study was to compare rat tissues with respect to their reactive oxygen and nitrogen species (RONS) generating activities as a function of age. We quantified the RONS generation in vivo in young (6 months) and in old (30 months) male Sprague-Dawley rats using the recently developed spin trap 1-hydroxy-3-carboxy-pyrrolidine, applied intravenously. This spin trap reacts with superoxide radical and peroxynitrite yielding a stable spin adduct which is detectable by means of electron paramagnetic resonance (EPR) spectroscopy in frozen tissues. In old rats RONS generation was significantly increased compared to their young counterparts in the following order: blood

Left ventricular lead position, mechanical activation, and myocardial scar in relation to left ventricular reverse remodeling and clinical outcomes after cardiac resynchronization therapy: A feature-tracking and contrast-enhanced cardiovascular magnetic resonance study.

BACKGROUND: Late mechanical activation (LMA) and viability in the left ventricular (LV) myocardium have been proposed as targets for LV pacing during cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to determine whether an LV lead position over segments with LMA and no scar improves LV reverse remodeling (LVRR) and clinical outcomes after CRT. METHODS: Feature-tracking and late gadolinium enhancement images were analyzed retrospectively in patients with heart failure (HF) (n = 89; mean age 66.8 ± 10.8 years; LV ejection fraction = 23.1% ± 9.9%) who underwent cardiovascular magnetic resonance (CMR) scanning before CRT implantation. Lead positions were classified as concordant (no scar and LMA [time to peak systolic circumferential strain]) or nonconcordant (scar and/or no LMA). RESULTS: LVRR occurred in 68% and 24% of patients with concordant and nonconcordant LV lead positions, respectively (P < .001). Over a median of 4.4 years (range 0.1-8.7 years), LV lead concordance predicted cardiac mortality (adjusted odds ratio [aOR] 0.27; 95% confidence interval [CI] 0.12-0.62) and cardiac mortality or HF hospitalizations (aOR 0.26, 95% CI 0.12-0.58). "No scar" in the paced segment predicted cardiac mortality (aOR 0.24; 95% CI 0.11-0.52) and cardiac mortality or HF hospitalizations (adjusted aOR 0.24; 95% CI 0.12-0.49). CONCLUSION: LV lead deployment over nonscarred LMA segments was associated with better LVRR and clinical outcomes after CRT. LVRR was primarily related to LMA, whereas events were primarily related to scar. These findings support the use of late gadolinium enhancement CMR and feature-tracking CMR in guiding LV lead deployment.

Mechanisms of vasodilatation induced by nitrite instillation in intestinal lumen: possible role of hemoglobin.

It has been shown that nitrite can be reduced to nitric oxide (NO) in intestine and a number of other tissues and released into the blood to form nitrosylhemoglobin (NO-Hb), existing in an equilibrium with S-nitrosohemoglobin. The latter has been suggested to be an NO transporter to distant organs. The aim of this study was to define the pathway of nitrite reduction to form NO in intestinal wall and to estimate whether this pathway has an effect on peripheral circulation. We have shown that in rat intestine at pH 7.0 70% of nitrite is converted to NO in mitochondria. At pH 6.0, nonenzymatic nitrite reduction becomes as efficient as the mitochondrial pathway. To prove whether the NO formed from nitrite in intestine can induce vasodilatation, sodium nitrite was instilled into intestinal lumen and the concentration of NO formed and diffused into the blood was followed by measuring of NO-Hb complex formation. We found that the concentration of NO-Hb gradually increases with the increase of nitrite concentration in intestinal lumen. However, it was not always accompanied by a decrease in systemic blood pressure. Blood pressure dropped down only after NO-Hb reached a threshold concentration of approximately 10 microM. These data show that NO-Hb cannot provide enough NO for vasodilatation if the concentration of NO bound to Hb is < 10 microM. The exact mechanism underlying vasodilatation observed when the concentration of NO-bound Hb was > 10 microM is, however, not clear yet and requires further studies.

Myocardial strain measurement with feature-tracking cardiovascular magnetic resonance: normal values.

AIMS: Myocardial deformation is a key to clinical decision-making. Feature-tracking cardiovascular magnetic resonance (FT-CMR) provides quantification of motion and strain using standard steady-state in free-precession (SSFP) imaging, which is part of a routine CMR left ventricular (LV) study protocol. An accepted definition of a normal range is essential if this technique is to enter the clinical arena. METHODS AND RESULTS: One hundred healthy individuals, with 10 men and women in each of 5 age deciles from 20 to 70 years, without a history of cardiovascular disease, diabetes, renal impairment, or family history of cardiovascular disease, and with a normal stress echocardiogram, underwent FT-CMR assessment of LV myocardial strain and strain rate using SSFP cines.Peak systolic longitudinal strain (Ell) was -21.3 ± 4.8%, peak systolic circumferential strain (Ecc) was -26.1 ± 3.8%, and peak systolic radial strain (Err) was 39.8 ± 8.3%. On Bland-Altman analyses, peak systolic Ecc had the best inter-observer agreement (bias 0.63 ± 1.29% and 95% CI -1.90 to 3.16) and peak systolic Err the least inter-observer agreement (bias 0.13 ± 6.41 and 95% CI -12.44 to 12.71). There was an increase in the magnitude of peak systolic Ecc with advancing age, which was greatest in subjects over the age of 50 years (R(2) = 0.11, P = 0.003). There were significant gender differences (P < 0.001) in peak systolic Ell, with a greater magnitude of deformation in females (-22.7%) than in males (-19.3%). CONCLUSION: Normal values for myocardial strain measurements using FT-CMR are provided. All circumferential and longitudinal based variables had excellent intra- and inter-observer variability.

Epr analysis reveals three tissues responding to endotoxin by increased formation of reactive oxygen and nitrogen species.

The excessive formation of reactive oxygen and nitrogen species (RONS) in tissue has been implicated in the development of various diseases. In this study we adopted ex vivo low temperature EPR spectroscopy combined with spin trapping technique to measure local RONS levels in frozen tissue samples. CP-H (1-hydroxy-3-carboxy-pyrrolidine), a new nontoxic spin probe, was used to analyze RONS in vivo. In addition, nitrosyl complexes of hemoglobin were determined to trace nitric oxide released into blood. By this technique we found that RONS formation in tissue of control animals increased in the following order: liver < heart < brain < cerebellum < lung < muscle < blood < ileum < kidney < duodenum < jejunum. We also found that endotoxin challenge, which represents the most common model of septic shock, increased the formation of RONS in rat liver, heart, lung, and blood, but decreased RONS formation in jejunum. We did not find changes in RONS levels in other parts of gut, brain, skeletal muscles, and kidney. Scavenging of RONS by CP-H was accompanied by an increase in blood pressure, indicating that LPS-induced vasodilatation may be due to RONS, but not due to nitric oxide. Experiments with tissue homogenates incubated in vitro with CP-H showed that ONOO(-) and O(2)(*)(-), as well as other not identified RONS, are detectable by CP-H in tissue. In summary, low-temperature EPR combined with CP-H infusion allowed detection of local RONS formation in tissues. Increased formation of RONS in response to endotoxin challenge is organ specific.