Beth Unsworth

First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study.

BACKGROUND Sympathetic overactivation, is reduced by renal denervation in drug-resistant hypertension. A similar role for renal denervation in heart failure remains unstudied, partly due to the concern about potential concomitant deleterious blood pressure reductions. This pilot study evaluated the safety of renal denervation for heart failure using an intensive follow-up protocol. METHOD 7 patients (mean age 69 years) with chronic systolic heart failure (mean BP on referral 112/65 mmHg) on maximal tolerated heart failure therapy underwent bilateral renal denervation May-July 2011. Patients were admitted for pre-procedure baseline assessments and in-patient observation for 5 days following denervation. Follow-up was weekly for 4 weeks, and then monthly for 6 months. RESULTS No significant haemodynamic disturbances were noted during the acute phase post renal denervation. Over 6 months there was a non-significant trend to blood pressure reduction (Δsystolic -7.1 ± 6.9 mmHg, p=0.35; Δdiastolic -0.6 ± 4.0 mmHg, p=0.88). No hypotensive or syncopal episodes were reported. Renal function remained stable (Δcreatinine -5.7 ± 8.4 μmol/l, p=0.52 and Δurea -1.0 ± 1.0 mmol/l, p=0.33). All 7 patients described themselves as symptomatically improved. The six minute walk distance at six months was significantly increased (Δ=27.1 ± 9.7 m, p=0.03), with each patient showing an increase. CONCLUSIONS This study found no procedural or post procedural complications following renal denervation in patients with chronic systolic heart failure in 6 months of intensive follow-up. Results suggested improvements in both symptoms and exercise capacity, but further randomised, blinded sham-controlled clinical trials are required to determine the impact of renal denervation on morbidity and mortality in systolic heart failure. These data suggest such trials will be safe. ClinicalTrial.gov NCT01584700

The right ventricular annular velocity reduction caused by coronary artery bypass graft surgery occurs at the moment of pericardial incision

Background Right ventricular (RV) long-axis function is known to be depressed after cardiac surgery, but the mechanism is not known. We hypothesized that intraoperative transesophageal echocardiography could pinpoint the time at which this happens to help narrow the range of plausible mechanisms. Method Transthoracic echocardiography was conducted in 33 patients before and after elective coronary artery bypass graft. In an intensively monitored cohort of 9 patients, we also monitored RV function intraoperatively using serial pulsed wave tissue Doppler (PW TD) transesophageal echocardiography. Results There was no significant difference in myocardial velocities from the onset of the operation up to the beginning of pericardial incision, change in RV PW TD S′ velocities 3% ± 2% (P = not significant). Within the first 3 minutes of opening the pericardium, RV PW TD S′ velocities had reduced by 43% ± 17% (P < .001). At 5 minutes postpericardial incision, 2 minutes later, the velocities had more than halved, by 54% ± 11% (P < .0001). Velocities thereafter remained depressed throughout the operation, with final intraoperative S′ reduction being 61% ± 11% (P < .0001). One month after surgery, in the full 33-patient cohort, transthoracic echocardiogram data showed a 55% ± 12% (P < .0001) reduction in RV S′ velocities compared with preoperative values. Conclusions Minute-by-minute monitoring during cardiac surgery reveals that, virtually, all the losses in RV systolic velocity occurs within the first 3 minutes after pericardial incision. Right ventricular long-axis reduction during coronary bypass surgery results not from cardiopulmonary bypass but rather from pericardial incision.

Contrasting effect of different cardiothoracic operations on echocardiographic right ventricular long axis velocities, and implications for interpretation of post-operative values

Background Patients undergoing coronary artery bypass grafting (CABG) experience a reduction in right ventricular long axis velocities post surgery. Objectives We tested whether the phenomenon of right ventricular (RV) long axis velocity decline depends on the chest being opened fully by mid-line sternotomy, pericardial incision, or on the type of operation performed. Method By intraoperative transoesophageal echocardiography (TEE) we recorded serial right ventricular (RV) systolic pulse-wave tissue Doppler velocities during 6 types of elective procedure: 53 CABG surgery, 15 robotic-assisted minimally-invasive CABG (RCABG), 28 aortic valve replacement (AVR), 8 minimally-invasive aortic valve replacement (mini-AVR), 5 mediastinal mass excision, and 1 left atrial myxoma excision. Pre and post operative transthoracic echocardiography (TTE) were also conducted. Results Surgery without substantial opening of the pericardium did not significantly reduce RV systolic velocities (RCABG 13 ± 1.8 versus 12.4 ± 2.7 cm/s post; mini-AVR 11.9 ± 2.3 versus 11.1 ± 2.3 cm/s; mediastinal mass excision 13.9 ± 3.1 versus 13.8 ± 4 cm/s). In contrast, within 5 min of pericardial incision those whose surgery involved full opening of the pericardium had large reductions in RV velocities: 54 ± 11% decline with CABG (11.3 ± 1.9 to 5.1 ± 1.6 cm/s, p < 0.0001), 54 ± 5% with AVR (12.6 ± 1.4 to 5.7 ± 0.6 cm/s, p < 0.001) and 49% with left atrial myxoma excision (11.3 to 15.8 cm/s). This persisted immediately after pericardial opening to the end of surgery (61 ± 11%, p < 0.0001; 58 ± 7%, p < 0.0001; 59% respectively). Conclusions It is full opening of the pericardium, and not cardiac surgery in general, which causes RV long axis decline following cardiac surgery. The impact is immediate (within 5 min) and persistent.

Influence of gender on clinical outcomes following transcatheter aortic valve implantation from the UK transcatheter aortic valve implantation registry and the National Institute for Cardiovascular Outcomes Research.

Gender differences exist in outcomes after percutaneous coronary intervention and coronary artery bypass graft surgery but have yet to be fully explored after transcatheter aortic valve implantation. We aimed to investigate gender differences after transcatheter aortic valve implantation in the UK National Institute for Cardiovascular Outcomes Research registry. A retrospective analysis was performed of Medtronic CoreValve and Edwards SAPIEN implantation in 1,627 patients (756 women) from January 2007 to December 2010. Men had more risk factors: poor left ventricular systolic function (11.9% vs 5.5%, p <0.001), 3-vessel disease (19.4% vs 9.2%, p <0.001), previous myocardial infarction (29.5% vs 13.0%, p <0.001), peripheral vascular disease (32.4% vs 23.3%, p <0.001), and higher logistic EuroSCORE (21.8 ± 14.2% vs 21.0 ± 13.4%, p = 0.046). Thirty-day mortality was 6.3% (confidence interval 4.3% to 7.9%) in women and 7.4% (5.6% to 9.2%) in men and at 1 year, 21.9% (18.7% to 25.1%) and 22.4% (19.4% to 25.4%), respectively. There was no mortality difference: p = 0.331 by log-rank test; hazard ratio for women 0.91 (0.75 to 1.10). Procedural success (96.6% in women vs 96.4% in men, p = 0.889) and 30-day cerebrovascular event rates (3.8% vs 3.7%, p = 0.962) did not differ. Women had more major vascular complications (7.5% vs 4.2%, p = 0.004) and less moderate or severe postprocedural aortic regurgitation (7.5% vs 12.5%, p = 0.001). In conclusion, despite a higher risk profile in men, there was no gender-related mortality difference; however, women had more major vascular complications and less postprocedural moderate or severe aortic regurgitation.

The Acute Effects of Changes to AV Delay on BP and Stroke Volume Potential Implications for Design of Pacemaker Optimization Protocols

Background— The AV delay optimization of biventricular pacemakers (cardiac resynchronization therapy) may maximize hemodynamic benefit but consumes specialist time to conduct echocardiographically. Noninvasive BP monitoring is a potentially automatable alternative, but it is unknown whether it gives the same information and similar precision (signal/noise ratio). Moreover, the immediate BP increment on optimization has been reported to decay away: it is unclear whether this is the result of an (undesirable) decrease in stroke volume or a (desirable) compensatory relief of peripheral vasoconstriction. Methods and Results— To discriminate between these alternative mechanisms, we measured simultaneous beat-to-beat stroke volume (flow) using Doppler echocardiography, and BP using finger photoplethysmography, during and after AV delay changes from 40 to 120 ms in 19 subjects with cardiac pacemakers. BP and stroke volume both increased immediately ( P <0.001, within 1 heartbeat). BP showed a clear decline a few seconds later (average rate, −0.65 mm Hg/beat; r =0.95 [95% CI, 0.86–0.98]); in contrast, stroke volume did not decline ( P =0.87). The immediate BP increment correlated strongly with the stroke volume increment ( r =0.74, P <0.001). The signal/noise ratio was 3-fold better for BP than stroke volume (6.8±3.5 versus 2.3±1.4; P <0.001). Conclusions— Improving AV delay immediately increases BP, but the effect begins to decay within a few seconds. Reassuringly, this is because of compensatory vasodilatation rather than reduction in cardiac function. Pacemaker optimization will never be reliable unless there is an adequate signal/noise ratio. Using BP rather than Doppler minimizes noise. The early phase (before vascular compensation) has the richest signal lode.Background— The AV delay optimization of biventricular pacemakers (cardiac resynchronization therapy) may maximize hemodynamic benefit but consumes specialist time to conduct echocardiographically. Noninvasive BP monitoring is a potentially automatable alternative, but it is unknown whether it gives the same information and similar precision (signal/noise ratio). Moreover, the immediate BP increment on optimization has been reported to decay away: it is unclear whether this is the result of an (undesirable) decrease in stroke volume or a (desirable) compensatory relief of peripheral vasoconstriction. Methods and Results— To discriminate between these alternative mechanisms, we measured simultaneous beat-to-beat stroke volume (flow) using Doppler echocardiography, and BP using finger photoplethysmography, during and after AV delay changes from 40 to 120 ms in 19 subjects with cardiac pacemakers. BP and stroke volume both increased immediately (P<0.001, within 1 heartbeat). BP showed a clear decline a few seconds later (average rate, −0.65 mm Hg/beat; r=0.95 [95% CI, 0.86–0.98]); in contrast, stroke volume did not decline (P=0.87). The immediate BP increment correlated strongly with the stroke volume increment (r=0.74, P<0.001). The signal/noise ratio was 3-fold better for BP than stroke volume (6.8±3.5 versus 2.3±1.4; P<0.001). Conclusions— Improving AV delay immediately increases BP, but the effect begins to decay within a few seconds. Reassuringly, this is because of compensatory vasodilatation rather than reduction in cardiac function. Pacemaker optimization will never be reliable unless there is an adequate signal/noise ratio. Using BP rather than Doppler minimizes noise. The early phase (before vascular compensation) has the richest signal lode.

Successful placement of left atrial appendage closure device is heavily dependent on 3-dimensional transesophageal imaging.

![Figure][1] [![Graphic][3] ][3] A 65-year-old man was referred for routine left atrial appendage (LAA) device closure (Watchman, Atritech, Inc., Plymouth, Minnesota). The patient had a history of atrial fibrillation, with a CHADS2 score of 2, warranting warfarin anticoagulation

Basal Septal Hypertrophy

A significant clinical problem is patients presenting with exercise-limiting dyspnoea, sometimes with associated chest pain, in the absence of detectable left ventricular (LV) systolic dysfunction, coronary artery disease, or lung disease. Often the patients are older, female, and have isolated basal septal hypertrophy (BSH), frequently on a background of mild hypertension. The topic of breathlessness in patients with clinical heart failure, but who have a normal ejection fraction (HFNEF) has attracted significant controversy over the past few years. This review aims to analyse the literature on BSH, identify the possible associations between BSH and HFNEF, and consequently explore possible pathophysiological mechanisms whereby clinical symptoms are experienced.

A systematic approach to designing reliable VV optimization methodology: Assessment of internal validity of echocardiographic, electrocardiographic and haemodynamic optimization of cardiac resynchronization therapy

Background In atrial fibrillation (AF), VV optimization of biventricular pacemakers can be examined in isolation. We used this approach to evaluate internal validity of three VV optimization methods by three criteria. Methods and results Twenty patients (16 men, age 75 ± 7) in AF were optimized, at two paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG (minimizing QRS duration). Each optimization method was evaluated for: singularity (unique peak of function), reproducibility of optimum, and biological plausibility of the distribution of optima. The reproducibility (standard deviation of the difference, SDD) of the optimal VV delay was 10 ms for pressure, versus 8 ms (p = ns) for QRS and 34 ms (p < 0.01) for flow. Singularity of optimum was 85% for pressure, 63% for ECG and 45% for flow (Chi2 = 10.9, p < 0.005). The distribution of pressure optima was biologically plausible, with 80% LV pre-excited (p = 0.007). The distributions of ECG (55% LV pre-excitation) and flow (45% LV pre-excitation) optima were no different to random (p = ns). The pressure-derived optimal VV delay is unaffected by the paced rate: SDD between slow and fast heart rate is 9 ms, no different from the reproducibility SDD at both heart rates. Conclusions Using non-invasive arterial pressure, VV delay optimization by parabolic fitting is achievable with good precision, satisfying all 3 criteria of internal validity. VV optimum is unaffected by heart rate. Neither QRS minimization nor LVOT VTI satisfy all validity criteria, and therefore seem weaker candidate modalities for VV optimization. AF, unlinking interventricular from atrioventricular delay, uniquely exposes resynchronization concepts to experimental scrutiny.

Recognising bicuspid aortic stenosis in patients referred for transcatheter aortic valve implantation: routine screening with three-dimensional transoesophageal echocardiography

Severe aortic valve stenosis was discovered incidentally during preoperative workup for hernia repair in a 78-year-old man. He was deemed high risk for conventional surgical aortic valve replacement because of poor lung function and was consequently assessed for transcatheter aortic valve implantation (TAVI). An initial transthoracic echocardiogram was performed to confirm the leaflet insertion diameter. Although heavily calcified, the aortic annular region was clearly visualised and a leaflet insertion diameter of 24 mm was recorded (panel A …

Novel use of cardiac pacemakers in heart failure to dynamically manipulate the respiratory system through algorithmic changes in cardiac output.

Background—Alternation of heart rate between 2 values using a pacemaker generates oscillations in end-tidal CO2 (et-CO2). This study examined (a) whether modulating atrioventricular delay can also do this, and (b) whether more gradual variation of cardiac output can achieve comparable changes in et-CO2 with less-sudden changes in blood pressure. Methods and Results—We applied pacemaker fluctuations by adjusting heart rate (by 30 bpm) or atrioventricular delay (between optimal and nonoptimal values) or both, with period of 60 s in 19 heart failure patients (age 73±11, EF 29±12%). The changes in cardiac output, by either heart rate or atrioventricular delay or both, were made either as a step (“square wave”) or more gradually (“sine wave”). We obtained changes in cardiac output sufficient to engender comparable oscillations in et-CO2 (P=NS) in all 19 patients either by manipulation of heart rate (14), or by atrioventricular delay (2) or both (3). The square wave produced 191% larger and 250% more sudden changes in blood pressure than the sine wave alternations (22.4±11.7 versus 13.6±4.5 mm Hg, P<0.01 and 19.8±10.0 versus 7.9±3.2 mm Hg over 5 s, P<0.01), but peak-to-trough et-CO2 elicited was only 45% higher (0.45±0.18 versus0.31±0.13 kPa, P=0.01). Conclusion—This study shows that cardiac output is the key to dynamically manipulating the respiratory system with pacing sequences. When manipulating respiration by this route, a sine wave pattern may be preferable to a square wave, because it minimizes sudden blood pressure fluctuations.