Impact of diastolic dysfunction on long-term mortality and quality of life after transcatheter aortic valve replacement.

BACKGROUND: There is conflicting data as to whether diastolic dysfunction (DD) affects the prognosis of patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). METHODS: Consecutive patients undergoing TAVR underwent assessment of DD with preoperative echocardiography and NT-pro BNP. Long-term survival was ascertained every 6 months by clinic visits or phone. DD was graded according to the new American Society of Echocardiography recommendations. Health status was assessed at baseline and 30 days post-procedure using the KCCQ-12 questionnaire. Long-term survival was displayed using Kaplan-Meier curves according to NT-pro BNP levels and DD grades. RESULTS: We included 222 patients, mean age 78 (±8) years, median STS score 4 (interquartile range = 3-7), median follow-up time 385 days (IQR = 180-640). DD was absent in 25, Grade I in 13, Grade II in 74, Grade III in 24, and indeterminate in 86 patients. Advanced (Grades II-III) DD was associated with higher pre-procedural NT-pro BNP levels (p < .001), worse quality of life (p < .001) but similar surgical risk (p = .43). Advanced and indeterminate DD were associated with increased long-term mortality (25-28% vs. 5%, p = .02) and elevated NT-pro BNP levels (26.4% vs. 9.8%, p = .05). Improvements in quality of life measures were seen in all DD groups (median change in KCCQ score no or Grade I DD:14 [3-21] vs. Grades II-III DD: 15 [16-26; p = .37]). CONCLUSION: Preoperative NT-pro BNP levels and echocardiographic indices of indeterminate or advanced DD are associated with increased long-term mortality after TAVR but similar improvements in quality of life.

Utility of nuclear stress imaging in predicting long-term outcomes one-year post CABG Surgery.

BACKGROUND: Early MPI after CABG is currently considered rarely appropriate in asymptomatic patients. This study aimed to identify prognostic value of nuclear stress-imaging post-CABG. METHODS: This was a single center prospective study looking at long-term outcomes post-CABG. Per protocol participants underwent SPECT-MPI stress testing and coronary angiogram on the same day, 1-year following CABG. Defect size was semi-quantified. The primary outcomes were the composite of death and congestive heart failure. RESULTS: Eighty-four participants underwent nuclear stress-imaging and angiography, with a median follow-up of 11.1 years. Three separate stress findings predicted the primary outcome: inability to reach stage 3 of a Bruce protocol (OR 7.3, CI 2.4-22.1, P < 0.001), LVEF < 45% (OR 4.0, CI 1.1-15.3, P = 0.041) and a moderate-large stress defect size (HR 2.31, CI 1.1-1.5, P = 0.04). These findings appear to be additive and strongest among patients who underwent exercise stress testing (HR 10.6, CI 3.6-30.6, P < 0.001). Graft disease was identified in 39 (46%) patients and compared to those individuals with no graft disease, did not predict long-term adverse outcomes (P = 0.29). CONCLUSION: In clinically stable patients early after revascularization with CABG, SPECT-MPI can identify patients at higher risk of heart failure and death.

NT-Pro BNP Predicts Myocardial Injury Post-vascular Surgery and is Reduced with CoQ10: A Randomized Double-Blind Trial.

BACKGROUND: NT-Pro BNP levels provide incremental value in perioperative risk assessment prior to major noncardiac surgery. Whether they can be pharmacologically modified in patients prior to an elective vascular operation is uncertain. METHODS: A double-blind, randomized controlled trial was implemented at a single institution. Patients were screened during their preoperative vascular clinic appointment and randomly assigned to CoQ10 (400 mg per day) versus Placebo for 3 days prior to surgery. Biomarkers, including NT-Pro BNP, troponin I and C-reactive protein were obtained prior to and following surgery for up to 48 hours. The primary endpoint was postoperative NT-Pro BNP levels, and secondary endpoint measures included myocardial injury, defined by an elevated cardiac troponin level and length of stay. RESULTS: One hundred and twenty-three patients were randomized to receive either CoQ10 (N = 62) versus Placebo (N = 61) for 3 days before vascular surgery. Preoperative cardiac risks included ischemic heart disease (N = 52), CHF (N = 12), stroke (N = 23), and diabetes mellitus (N = 48) and the planned vascular procedures were infrainguinal (N = 78), carotid (N = 36), and intraabdominal (N = 9). There were no intergroup differences in these clinical variables. NT-Pro BNP levels (median; IQs) in the CoQ10 and Placebo groups were 179 (75-347) and 217 (109-585) pg/ml, respectively, (P = 0.08) preoperatively, and 397 (211-686) and 591 (288-1,433) pg/ml respectively, (P = 0.01) at 24 hours following surgery. Patients with an elevated NT-Pro BNP had a higher incidence of myocardial injury, (58% vs. 20%; P < 0.01) and a longer hospital stay (4.4 ± 3.8 vs. 2.8 ± 3.2 days; P < 0.02) compared with individuals without an elevated NT-Pro BNP level. CONCLUSIONS: NT-Pro BNP levels predict adverse events post-vascular surgery and are lowered in those patients assigned to preoperative administration of CoQ10. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03956017. Among patients undergoing elective vascular surgery, 123 patients were randomized to either CoQ10 (400 mg/day) versus placebo for three days preoperatively. NT-Pro BNP levels (median; IQs) in the CoQ10 and Placebo groups were 179 (75-347) and 217 (109-585) pg/ml, respectively, (P = 0.08) preoperatively, and 397 (211-686) and 591 (288-1,433) pg/ml, respectively, (P = 0.01) post-surgery. Patients with an elevated NT-Pro BNP had a higher incidence of myocardial injury (58% vs. 20%; P < 0.01) and a longer hospital stay (4.4 ± 3.8 vs. 2.8 ± 3.2 days; P < 0.02) compared with individuals without an NT-Pro BNP elevation. In conclusion, BNP predicts adverse outcomes and can be reduced with preoperative CoQ10.

Utility of nuclear stress imaging for detecting coronary artery bypass graft disease.

BACKGROUND: The value of single photon emission computed tomography stress myocardial perfusion imaging (SPECT-MPI) for detecting graft disease after coronary artery bypass surgery (CABG) has not been studied prospectively in an unselected cohort. METHODS: Radial Artery Versus Saphenous Vein Graft Study is a Veterans Affairs Cooperative Study to determine graft patency rates after CABG surgery. Seventy-nine participants agreed to SPECT-MPI within 24 hours of their coronary angiogram, one-year after CABG. The choice of the stress protocol was made at the discretion of the nuclear radiologist and was either a symptom-limited exercise test (n = 68) or an adenosine infusion (n = 11). The SPECT-MPI results were interpreted independent of the angiographic results and estimates of sensitivity, specificity and accuracy were based on the prediction of a graft stenosis of ≥70% on coronary angiogram. RESULTS: A significant stenosis was present in 38 (48%) of 79 patients and 56 (22%) of 251 grafts. In those stress tests with an optimal exercise heart rate response (>80% maximum predicted heart rate) (n = 26) sensitivity, specificity and accuracy of SPECT-MPI for predicting the graft stenosis was 77%, 69% and 73% respectively. With adenosine (n = 11) it was 75%, 57% and 64%, respectively. Among participants with a suboptimal exercise heart rate response, the sensitivity of SPECT-MPI for predicting a graft stenosis was <50%. The accuracy of SPECT-MPI for detecting graft disease did not vary significantly with ischemic territory. CONCLUSIONS: Under optimal stress conditions, SPECT-MPI has a good sensitivity and accuracy for detecting graft disease in an unselected patient population 1 year post-CABG.

Increased baseline ECG R-R dispersion predicts improvement in systolic function after atrial fibrillation ablation.

Background: Atrial fibrillation (AF) is associated with left ventricular (LV) systolic dysfunction which may improve after AF ablation. We hypothesised that increased ventricular irregularity, as measured by R-R dispersion on the baseline ECG, would predict improvement in the left ventricular ejection fraction (LVEF) after AF ablation. Methods: Patients with LVEF <50% at two US centres (2007-2016), having both a preablation and postablation echocardiogram or cardiac MRI, were included. LVEF improvement was defined as absolute increase in LVEF by >7.5%. Multivariable logistic regression (restricted to echocardiographic/ECG variables) was performed to evaluate predictors of LVEF improvement. Results: Fifty-two patients were included in this study. LVEF improved in 30 patients (58%) and was unchanged/worsened in 22 patients (42%). Those with versus without LVEF improvement had an increased baseline R-R dispersion (645±155 ms vs 537±154 ms, p=0.02, respectively). The average baseline heart rate in all patients was 93 beats per minute. After multivariable logistic regression, increased R-R dispersion (OR 1.59, 95% CI 1.00 to 2.55, p=0.03) predicted LVEF improvement. Conclusions: Increased R-R dispersion on ECG was independently associated with improved systolic function after AF ablation. This broadens the existing knowledge of arrhythmia-induced cardiomyopathy, demonstrating that irregular electrical activation (as measured by increased R-R dispersion on ECG) is associated with a cardiomyopathy capable of improving after AF ablation.

Electrophysiological characteristics and radiofrequency ablation of sustained monomorphic ventricular tachycardia in adult patients with isolated ventricular noncompaction.

PURPOSE: This study examined electrophysiological characteristics and outcomes of patients with sustained ventricular tachycardia (VT) in the setting of isolated ventricular noncompaction (IVNC). BACKGROUND: In patients with IVNC, VT has been associated with sudden cardiac death. However, the electrophysiological characteristics and optimal management of these VTs are only incompletely understood. METHODS: This retrospective cohort study assessed arrhythmia characteristics and outcomes in IVNC patients with sustained monomorphic VTs. Data were obtained from five academic centers covering the time period from January 1, 2006, to December 31, 2016, with a median follow-up of 40 months. RESULTS: Eighteen consecutive IVNC patients with sustained VTs (12 males [66%], mean age of 44.4 ± 16.9 years) were enrolled. Seven (39%) patients underwent VT ablation (five males, mean age of 43.3 ± 15.5 years) and nine (50%) patients received ICD therapy. Six of 18 patients (33%) died during a median follow-up of 40 months. Of these, three had ICDs, two had undergone VT ablation, and one had received only antiarrhythmic drugs. Among the seven patients with prior VT ablation, five VTs in the RV (three RVOT and one tricuspid annulus) and two LV VTs (one anterolateral papillary muscle and one inferolateral wall) were localized by 3-D mapping and successfully ablated. In six of seven ablation cases (85.7%), the VTs were distant from the noncompaction zone. VTs appeared to be focal in 57% (4/7) and macro-reentry in 43% (3/7) of patients based on 3-D mapping and entrainment studies. The success rate of VT ablation was 85.7% with one VT recurrence and two deaths during the mean follow-up of 54 (28-115) months. CONCLUSIONS: IVNC Patients with sustained VTs appear to have a poor prognosis despite receiving ICD or apparently successful VT ablation therapy. Further, most VTs appear to arise remote from the noncompaction zone. Whether these VTs were "idiopathic" or related to IVNC was uncertain.

The anti-malarial drug halofantrine and its metabolite N-desbutylhalofantrine block HERG potassium channels.

OBJECTIVE: The antimalarial drug halofantrine has been associated with QT interval prolongation and with fatal and nonfatal arrhythmias in patients without known underlying cardiac abnormalities. A common target for QT interval-prolonging drugs is the human ether-a-go-go gene (HERG) which encodes the pore forming subunit of the rapidly activating delayed rectifier K(+) current (I(Kr)). METHODS: We studied the effects of halofantrine (0.1-1000 nM) and its major metabolite N-desbutylhalofantrine (3-1000 nM) on wild type HERG K(+) channels stably expressed in HEK 293 cells, using the whole cell patch-clamp recording technique. RESULTS: Halofantrine and N-desbutylhalofantrine blocked HERG K(+) channels in a concentration-dependent manner with a half-maximal inhibitory concentration of 21.6 nM (n=31 cells) and 71.7 nM (n=18 cells), respectively. The development of drug block for both halofantrine and N-desbutylhalofantrine required channel activation indicative of open and/or inactivated state block. Drug washout or cell hyperpolarization resulted in minimal current recovery consistent with virtually irreversible binding. Using a ventricular action potential voltage clamp protocol, halofantrine and N-desbutylhalofantrine block of HERG current was greatest during phases 2 and 3 of the action potential waveform. CONCLUSION: We conclude that both halofantrine and N-desbutylhalofantrine cause high affinity block of HERG K(+) channels. Although N-desbutylhalofantrine has been suggested to be a safer antimalarial agent compared to halofantrine, our results suggest that the gain in the safety margin for QT interval prolongation-related cardiotoxicity is minimal.

Genetic basis for the origin of cardiac arrhythmias: implications for therapy.

The recognition of the role that genetic abnormalities play in the generation of cardiac arrhythmias and sudden cardiac death has evolved enormously over the past decade. One result is new insight into underlying physiologic and pathophysiologic mechanisms. New therapies based on this evolving insight are being developed. This review summarizes recent discoveries with a focus on the genetic basis of cardiac arrhythmias and their implications for new therapies.