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Ventricular Tachycardia Ablation in the Elderly: An International Ventricular Tachycardia Center Collaborative Group AnalysisBackground: Successful ventricular tachycardia (VT) ablation is associated with improved survival in patients with heart failure. However, the safety and efficacy of VT ablation in the elderly, a population with higher competing nonsudden death risk and comorbidities, have not been well defined. Methods and Results: The International Ventricular Tachycardia Center Collaborative Study Group registry of 2061 patients who underwent VT ablation at 12 international centers was analyzed. Kaplan–Meier analysis was used to estimate survival of patients ≥70 years with and without VT recurrence. Of the 2049 patients who met inclusion criteria, 681 (33%) patients were ≥70 years of age (mean age, 75±4 years). Among these, 92% were men, 71% had ischemic VT, and 42% had VT storm at presentation. Mean (±SD) left ventricular ejection fraction was 30±11%. Compared with patients <70 years, patients ≥70 years had higher in-hospital (4.4% versus 2.3%; P=0.01) and 1-year mortality (15% versus 11%; P=0.002) but a similar incidence of VT recurrence at 1 year (26% versus 25%; P=0.74) and time to VT recurrence (280 versus 289 days; P=0.20). Absence of VT recurrence during follow-up was strongly associated with improved survival in patients ≥70 years. Conclusion: VT ablation in the elderly is feasible and reasonably safe with a modestly higher in-hospital and 1-year mortality, with similar rates of VT recurrence at 1 year compared with younger patients. Successful VT ablation, that is, lack of VT recurrence, is strongly associated with improved survival even in this elderly subgroup. Copyright 2017 American Heart Association, Inc.
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"Malignant" left ventricular hypertrophy identifies subjects at high risk for progression to asymptomatic left ventricular dysfunction, heart failure, and death: MESA (Multi-Ethnic Study of Atherosclerosis)Background: As heart failure (HF)‐associated morbidity and mortality continue to escalate, enhanced focus on prevention is increasingly important. “Malignant” left ventricular (LV) hypertrophy (LVH): LVH combined with an elevated cardiac biomarker reflecting either injury (high‐sensitivity cardiac troponin T), or strain (amino‐terminal pro‐B‐type natriuretic peptide) has predicted accelerated progression to HF. We sought to determine whether malignant LVH identified community‐dwelling adults initially free of cardiovascular disease at high risk of asymptomatic decline in LV ejection fraction or a clinical cardiovascular event. Methods and Results: A total of 4985 of 6814 individuals without prevalent cardiovascular disease underwent baseline cardiac magnetic resonance for LVH in combination with measurement of plasma high‐sensitivity cardiac troponin T and amino‐terminal pro‐B‐type natriuretic peptide as part of MESA (Multi‐Ethnic Study of Atherosclerosis) and were subsequently divided into 4 groups: (1) No LVH, no elevated biomarkers (n=2206; 44.3%); (2) No LVH, ≥1 elevated biomarkers (n=2275; 45.7%); (3) LVH, no elevated biomarkers (n=153; 3.0%); and (4) LVH, ≥1 elevated biomarkers (malignant LVH; n=351; 7.0%). Cardiac magnetic resonance was repeated 10 years later (n=2831) for assessment of LV ejection fraction <50%. Median follow‐up was 12.2 years. Malignant LVH was associated with 7.0‐, 3.5‐, and 2.6‐fold adjusted increases in incidence of HF, cardiovascular death, and asymptomatic LV dysfunction, respectively, versus group 1. New‐onset HF was predominately HF with reduced ejection fraction (9.5‐fold increase). Conclusions: Malignant LVH is predictive of progression to asymptomatic LV dysfunction, HF (particularly HF with reduced ejection fraction), and cardiovascular death. Consequently, malignant LVH represents a high‐risk phenotype among individuals without known cardiovascular disease, which should be targeted for increased surveillance and more‐aggressive therapies. Copyright 2018 The Authors.
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Characterization of angiotensin II and protein kinase C signalling pathways that regulate intracellular pH in neonatal rat ventricular myocytesAngiotensin II (AngII) exerts many functional effects on the heart through the activation of protein kinase C (PKC) to affect contractility, and growth. It is now known that PKC is a family of 11 isoforms designated {dollar}\alpha{dollar}, {dollar}\beta{dollar}I, {dollar}\beta{dollar}II, {dollar}\gamma{dollar}, {dollar}\delta{dollar}, {dollar}\epsilon{dollar}, {dollar}\xi{dollar}, {dollar}\eta{dollar}, {dollar}\theta{dollar}, {dollar}\lambda{dollar}, and {dollar}\mu{dollar}. To examine the effects of PKC on the heart, it was first necessary to characterize which isoforms are expressed in this tissue. A RT-PCR approach was developed to identify isoforms that would amplify regions of the target cDNA of all the PKC isozymes in a single reaction. Cardiac cDNA was RT-PCR amplified and the products analyzed by a combination of restriction mapping and DNA sequencing which revealed the presence of only the {dollar}\alpha{dollar}, {dollar}\delta{dollar}, {dollar}\epsilon{dollar}, {dollar}\eta{dollar}, and {dollar}\xi{dollar} isoforms cardiac myocytes. Since many cardioactive hormones modulate intracellular pH (pH{dollar}\sb{lcub}\rm i{rcub}{dollar}), the goal of this study was to determine if AngII and PKC altered pH{dollar}\sb{lcub}\rm i{rcub}{dollar} in cultured neonatal rat ventricular myocytes. pH{dollar}\sb{lcub}\rm i{rcub}{dollar} was monitored in single cells loaded with the fluorescent indicator c-SNARF-1 or BCECF. Superfusion with 100 nM TPA, a direct activator of PKC, induces an alkalinization of 0.06 {dollar}\pm{dollar} 0.01 pH unit and increased the initial rate of recovery from an imposed acid load by 2.20 {dollar}\pm{dollar} 0.36 fold. The alkalinization and transporter activation are HCO{dollar}\sb3\sp-{dollar}-independent and amiloride-sensitive indicating the involvement of the Na{dollar}\sp+{dollar}/H{dollar}\sp+{dollar} exchanger. Furthermore, Cl{dollar}\sp-{dollar} removal experiments revealed a TPA-stimulated 1.31 {dollar}\pm{dollar} 0.11 fold enhancement of the acid-loading HCO{dollar}\sb3\sp-{dollar}-/Cl{dollar}\sp-{dollar} exchanger. The increase in the Na{dollar}\sp+{dollar}/H{dollar}\sp+{dollar} activity compared to that of the HCO{dollar}\sb3\sp-{dollar}/Cl{dollar}\sp-{dollar} exchanger is consistent with the alkalinization observed. Stimulation of the myocytes with 100 nM AngII resulted in a rapid HCO{dollar}\sb3\sp-{dollar}-dependent, amiloride-insensitive alkalinization of 0.08 {dollar}\pm{dollar} 0.02 pH unit. AngII also increased the rate of acid extrusion by 3.67 {dollar}\pm{dollar} 0.50 fold in a HCO{dollar}\sb3\sp-{dollar}-dependent and Cl{dollar}\sp-{dollar}-independent manner, indicating the activation of the Na{dollar}\sp+{dollar}/HCO{dollar}\sb3\sp-{dollar}-symport. The AngII activation of the symport is mediated through an AT{dollar}\sb2{dollar}-like signalling pathway since the pH{dollar}\sb{lcub}\rm i{rcub}{dollar} response was blocked by the AT{dollar}\sb2{dollar} receptor antagonist, CGP 42112A, and was unaffected by the AT{dollar}\sb1{dollar} inactivator, DTT. Superfusion of the myocytes with 5 {dollar}\mu{dollar}M arachidonic acid (ARA) mimicked the AngII-mediated alkalinization, suggesting further that ARA may mediate the response. Moreover, the AngII- and the ARA-induced responses were blocked with staurosporine, a PKC inhibitor. In summary, AngII activates the Na{dollar}\sp+{dollar}/HCO{dollar}\sb3\sp-{dollar} symport through the AT{dollar}\sb2{dollar} pathway via ARA and possibly through PKC. Although TPA and AngII both alkalinize the cell, they do so through two distinct pathways, perhaps by activating different PKC isoforms.