Titration and Tolerability of Sacubitril/Valsartan for Patients With Heart Failure in Clinical Practice.

Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.

Reduced Uptake of Family Screening in Genotype-Negative Versus Genotype-Positive Long QT Syndrome.

The acceptance and yield of family screening in genotype-negative long QT syndrome (LQTS) remains incompletely characterized. In this study of family screening for phenotype-definite Long QT Syndrome (LQTS, Schwartz score ≥3.5), probands at a regional Inherited Cardiac Arrhythmia clinic were reviewed. All LQTS patients were offered education by a qualified genetic counselor, along with materials for family screening including electronic and paper correspondence to provide to family members. Thirty-eight qualifying probands were identified and 20 of these had family members who participated in cascade screening. The acceptance of screening was found to be lower among families without a known pathogenic mutation (33 vs. 77 %, p = 0.02). A total of 52 relatives were screened; fewer relatives were screened per index case when the proband was genotype-negative (1.7 vs. 3.1, p = 0.02). The clinical yield of screening appeared to be similar irrespective of gene testing results (38 vs. 33 %, p = 0.69). Additional efforts to promote family screening among gene-negative long QT families may be warranted.

Extensive Thrombosis Following Lead Extraction: Further Justification for Routine Post-operative Anticoagulation.

Lead extraction is becoming increasingly common as indications for pacing and ICD insertion expand. Periop management varies between extraction centers, and no clinical guidelines have addressed the need for perioperative anticoagulation. We report a case of massive thrombosis which occurred shortly after laser lead extraction and is undoubtedly related to the trauma of the extraction and ensuing hypercoagulabiilty. Routine post-operative anticoagulation has been advocated as a means to prevent access vein (subclavian) stenosis, but many centres do not employ a routine post-extraction anticoagulation strategy. Pulmonary embolism following lead extraction is a known complication of this procedure and late mortality following lead extraction is a significant and underappreciated problem. We propose that further research attention should be directed at addressing the issue of routine post-extraction anticoagulation.

Arteriovenous fistula formation after lead extraction.

The junction between the left brachiocephalic vein and the superior vena cava is a high-risk region during lead extraction. Venous laceration with hemodynamic collapse is the most feared complication arising in this region, but arteriovenous fistula formation after excimer laser extraction also has been reported. A case of arteriovenous fistula presenting 3 days after extraction with acute pulmonary edema is described. A continuous murmur was heard near the extraction site and invasive angiography demonstrated a left internal mammary artery to the brachiocephalic vein fistula, which was coiled. A new continuous murmur after lead extraction is the hallmark of this rare complication.

Cryoablation versus RF ablation for AVNRT: A meta-analysis and systematic review.

INTRODUCTION: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia referred for ablation. High success rates have been accompanied with a small risk of atrioventricular (AV) block. Cryoablation has been used as an alternative to radiofrequency (RF) ablation, but studies have been underpowered in comparing the 2 techniques. METHODS AND RESULTS: An electronic search and hand-search of reference lists for published and unpublished data was carried out. Comparative studies (cohort and randomized controlled trials) of RF versus cryoablation for AVNRT were identified independently by 2 reviewers. Searches were limited to English language human studies. The primary metameter was long-term AVNRT recurrence (>2 months postprocedure and ECG/electrophysiology study [EPS]-documented) and secondary metameters included acute procedural failure and AV block requiring pacing. A total of 5,617 patients in 14 trials were included in this systematic review. Acute procedural failure with cryoablation was slightly higher than with RF ablation, but the difference was not statistically significant (risk ratio [RR] 1.44 [95% confidence interval; CI 0.91-2.28], P = 0.12). Long-term recurrence was higher with cryoablation (RR 3.66 [95% CI 1.84-7.28], P = 0.0002) even after adjusting for larger (6 mm) cryocatheter tips, "insurance lesions" and longer (>6 months) follow-up duration. RF ablation for AVNRT was associated with permanent AV block in 0.75% of patients, but was not reported in any patients treated with cryoablation (n = 1066, P = 0.01). CONCLUSIONS: Cryoablation is a safe and effective treatment for AVNRT. Although late-recurrence is more common with cryoablation than with RF ablation, avoidance of permanent AVN block makes it an attractive option in patients where the avoidance of AV block assumes higher priority (such as children and young adults).

Neither diabetes nor glucose-lowering drugs are associated with mortality after noncardiac surgery in patients with coronary artery disease or heart failure.

BACKGROUND: It is unclear whether diabetes mellitus or use of particular glucose-lowering agents is associated with increased risk of mortality after noncardiac surgery in patients with known cardiac disease. METHODS: We carried out a retrospective cohort study using 4 linked administrative databases in the province of Alberta, Canada from 1999-2006. RESULTS: Of the 32,834 patients with known cardiac disease in our cohort, 9305 (28%) had diabetes. All-cause 30-day mortality after noncardiac surgery was 6.4% in patients with diabetes, and 6.1% in those without diabetes (multivariate adjusted odds ratio [aOR] 0.97, 95% confidence interval [CI], 0.87-1.08). In the 24,037 patients older than 65, mortality was 7.5% in individuals with diabetes and 7.5% in those without diabetes (5.7% in those taking insulin [aOR, 0.89; 95% CI, 0.70-1.13], 8.0% in those using oral agents only [aOR, 1.08; 95% CI, 0.95-1.22]). None of the glucose-lowering drug classes were associated with perioperative mortality in elderly cardiac patients (sulfonylureas aOR, 0.94; 95% CI, 0.76-1.16; metformin aOR, 0.92; 95% CI, 0.74-1.14; thiazolidinediones aOR, 0.64; 95% CI, 0.40-1.04; insulin aOR, 0.83; 95% CI, 0.65-1.08), but use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (aOR, 0.83; 95% CI, 0.75-0.93), ß-blockers (aOR, 0.82; 95% CI, 0.72-0.93), or statins (aOR, 0.65; 95% CI, 0.55-0.78) in the 100 days before surgery were associated with lower 30-day mortality. CONCLUSIONS: Neither diabetes nor exposure to common classes of glucose-lowering drugs preoperatively were associated with increased perioperative mortality in cardiac patients undergoing noncardiac surgery. However, cardiac patients not using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, or statins preoperatively exhibited higher mortality rates, emphasizing the importance of optimizing evidence-based therapy before elective surgery in these patients.

Atrial septal defect closure in the elderly is associated with excellent quality of life, functional improvement, and ventricular remodelling.

BACKGROUND: While atrial septal defect (ASD) closure is known to improve morbidity and mortality in children and adults, data are only beginning to emerge about its role in elderly cohorts. The goals of this study were to compare outcomes after device or surgical closure of ASDs in the elderly, and to quantitatively assess quality of life. METHODS: Patients>60 years old who underwent ASD repair were studied. Functional status, arrhythmia burden, biventricular size and function were compared before and after ASD closure. Quality of life after ASD closure was assessed with the RAND SF-36 instrument. RESULTS: Sixty-seven patients, mean age of 68 years (range 60-86 years), were followed for 3.3 years. Nineteen percent underwent surgical closure and 81% underwent device closure. Major complication rates were 23% and 7% respectively with no procedure- related deaths. After surgical and device closure, quality of life was comparable to age-matched healthy controls, right ventricular end-diastolic dimension decreased by 10 mm (P<0.001), left ventricular end-diastolic dimension increased by 4 mm (P=0.001), biventricular function improved (right ventricular, P<0.001; left ventricular, P=0.007) and New York Heart Association class improved (P<0.001). Prevalence of atrial arrhythmias however, was unchanged. Beneficial effects were similar for patients treated surgically or with device closure. CONCLUSIONS: Given the favorable structural, functional, and quality of life outcomes after ASD closure in the elderly, advanced age alone should not be a contraindication to recommending surgical or device closure of an ASD.

A rapid PSA half-life following docetaxel chemotherapy is associated with improved survival in hormone refractory prostate cancer.

INTRODUCTION: Docetaxel chemotherapy prolongs survival in metastatic hormone-refractory prostate cancer (mHRPC), but many patients fail to respond to this therapy and there is potential for serious toxicity. Patients differ in their percent prostate-specific antigen (PSA) decline and rate of PSA decline following treatment. We propose that patients who achieve a rapid rate of PSA decline, measured as a shorter PSA half-life (PSAHL), may experience a longer overall survival (OS) than those who achieve a slower rate of PSA decline. METHODS: A chart review of patients treated with docetaxel for mHRPC in Alberta from January 2000 to May 2006 was performed. At 42 days (after 2 cycles) and 84 days (after 4 cycles) following chemotherapy, PSA response and PSAHL were determined. PSAHL could only be determined in patients with a PSA drop from baseline. Optimal PSAHL values for OS stratification were determined using the log-rank chi-square statistic. Survival analysis was carried out using Kaplan-Meier curves and regression analysis. RESULTS: There were 154 patients who fulfilled the inclusion criteria. Using 42-day postdocetaxel data, no associations with OS could be demonstrated. Using 84-day postdocetaxel data, patients stratified by PSAHL demonstrated a significant difference in OS (15 months vs. 25 months) and this relationship remained following multivariate analysis (hazard ratio 0.08 [0.021-0.34]). CONCLUSION: A more rapid rate of PSA decline (PSAHL <70 days) measured after 4 cycles of chemotherapy was associated with a longer OS. This result was independent of other known markers of survival and allowed for a greater survival differentiation than PSA response.