Simon W. Davies

Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: the U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry.

OBJECTIVES The objective was to define the characteristics of a real-world patient population treated with transcatheter aortic valve implantation (TAVI), regardless of technology or access route, and to evaluate their clinical outcome over the mid to long term. BACKGROUND Although a substantial body of data exists in relation to early clinical outcomes after TAVI, there are few data on outcomes beyond 1 year in any notable number of patients. METHODS The U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry was established to report outcomes of all TAVI procedures performed within the United Kingdom. Data were collected prospectively on 870 patients undergoing 877 TAVI procedures up until December 31, 2009. Mortality tracking was achieved in 100% of patients with mortality status reported as of December 2010. RESULTS Survival at 30 days was 92.9%, and it was 78.6% and 73.7% at 1 year and 2 years, respectively. There was a marked attrition in survival between 30 days and 1 year. In a univariate model, survival was significantly adversely affected by renal dysfunction, the presence of coronary artery disease, and a nontransfemoral approach; whereas left ventricular function (ejection fraction <30%), the presence of moderate/severe aortic regurgitation, and chronic obstructive pulmonary disease remained the only independent predictors of mortality in the multivariate model. CONCLUSIONS Midterm to long-term survival after TAVI was encouraging in this high-risk patient population, although a substantial proportion of patients died within the first year.

Reduction of mismatch of global ventilation and perfusion on exercise is related to exercise capacity in chronic heart failure.

BACKGROUND--The inability to match lung perfusion to ventilation because of a reduced cardiac output on exercise contributes to reduced exercise capacity in chronic heart failure. OBJECTIVE--To quantify ventilation to perfusion matching at rest and at peak exercise in patients with chronic heart failure and relate this to haemodynamic and ventilatory variables of exercise capacity. DESIGN--Eight men in New York Heart Association class II underwent maximal bicycle ergometry with expired gas analysis. MAIN OUTCOME MEASURES--On separate days, ventilation and perfusion gamma camera imaging was performed at rest, and at 80% of previous peak exercise heart rate during bicycle ergometry. The vertical distribution of mismatch between ventilation and perfusion (V/Q) was estimated from subtracted profiles of activity (ventilation and perfusion) to derive a numerical index of global mismatch. RESULTS--Maximal mean (SD) oxygen consumption on bicycle ergometry was 16.0 (4.5) ml min-1 kg-1. There was a reduction in the global V/Q mismatch index from 23.96 (5.90) to 14.88 (7.90) units (p < 0.01) at rest and at peak exercise. Global V/Q mismatch index at peak exercise correlated negatively with maximal minute ventilation (R = -0.90, p < 0.01) and with maximal mean arterial pressure (R = -0.79, p < 0.05), although no relation was seen with maximal oxygen consumption. The reduction in global V/Q mismatch index from rest to peak exercise correlated with maximal oxygen consumption (R = 0.88, p < 0.01), and with maximal minute ventilation (R = 0.87, p < 0.01). CONCLUSIONS--During exercise in patients with chronic heart failure, there is a reduction in the global V/Q mismatch index. A lower global V/Q mismatch index at peak exercise is associated with higher maximal ventilation. The reduction in global V/Q mismatch index on exercise correlates well with maximal exercise capacity. This may imply that the inability to perfuse adequately all regions of lung on exercise and match this to ventilation is a factor determining exercise capacity in chronic heart failure.

Effects of acute coronary occlusion and previous ischaemic injury on left ventricular wall motion in humans.

OBJECTIVE: To assess the acute effects of single and repeated coronary artery occlusions, during percutaneous transluminal coronary angioplasty (PTCA), on left ventricular long axis function in patients with stable and unstable angina. DESIGN: Prospective examination of ventricular systolic and diastolic long axis function using M mode echocardiography and transmitral Doppler in patients with significant coronary artery stenosis and either stable or unstable angina, during routine PTCA. SETTING: A tertiary referral centre for heart disease with cardiac catheterisation and echocardiographic facilities. SUBJECTS: 36 patients, age (SD) 60 (8) years, with significant coronary artery disease undergoing PTCA (mean duration 100-130 seconds) to the left anterior descending coronary artery (LAD) in 18 patients, native LAD or its vein graft in eight, and right coronary artery in 10. Controls were 21 normal subjects, age 58 (11) years. RESULTS-AT BASELINE: in systole, total long axis excursion was reduced at septal, posterior, and right sites in patients with LAD disease, at right site in those with vein grafts, and at septal and right sites in patients with right coronary artery disease. Peak shortening rate was often reduced in all patients and onset of shortening delayed with respect to the Q wave in patients with LAD disease. In diastole, onset of lengthening was always delayed, peak lengthening rate reduced, and relative A wave amplitude increased in all patients. There was a consistent abnormal shortening of the long axis during the isovolumic relaxation period in the 14 patients with unstable angina, not seen in the others. Transmitral A wave velocity was also increased and the onset of E wave delayed with respect to A2. At first balloon inflation: the extent of pre-existing systolic and particularly diastolic abnormalities consistently increased in patients with LAD or right coronary artery occlusion. This was associated with further delay in the onset of the transmitral Doppler E wave as its peak velocity fell and E/A ratio increased. In unstable angina, balloon inflation caused minor changes only in systolic function and no change in diastolic function. At second balloon inflation: systolic changes were the same as with the first inflation, while diastolic changes were attenuated by 10-15%. CONCLUSIONS: In stable angina intracoronary balloon inflation aggravated pre-existing systolic and diastolic abnormalities in the territory of the occluded vessel, indicating the dependence of both on coronary flow. In unstable angina balloon inflation caused only minor deterioration in systolic function, and diastolic changes-including the characteristic abnormal shortening during isovolumic relaxation-were unaffected. Thus resting abnormalities of left ventricular function in unstable angina are effectively dissociated from acute changes in coronary flow. Overall, the severity of systolic disturbances was unaltered by a second balloon inflation, but diastolic disturbances were attenuated by 10-15%, compatible with ischaemic preconditioning or recruitment of collaterals.

Reduced pulmonary microvascular permeability in severe chronic left heart failure

Pulmonary edema is a serious complication of heart failure, but often patients with chronic heart failure resist pulmonary edema despite elevated pulmonary venous pressures. This protection might be a result of decreased pulmonary microvascular permeability. Double-isotope scintigraphy with 113mindium-labeled transferrin and 99mtechnetium-labeled erythrocytes allows noninvasive estimation of pulmonary microvascular permeability; an index of transferrin accumulation is calculated that reflects microvascular permeability. Fourteen patients with severe chronic left ventricular dysfunction were compared with a control group of 15 patients with mild coronary artery disease. In the control group the transferrin accumulation index was 0.35 (range -0.3 to 1.0) x 10(-3)/min, and in patients with heart failure the index was 0.0 (range -1.0 to 0.7) x 10(-3)/min, which was significantly lower (p less than 0.01). The reduction in the transferrin accumulation index correlated weakly with the duration of heart failure (R = -0.5, p less than 0.02). These data indicate reduced protein efflux consistent with a decrease in pulmonary microvascular permeability in patients with severe chronic heart failure. Similar changes have been observed in severe mitral stenosis and may reflect a generalized adaptation to chronic pulmonary venous hypertension.

OVERNIGHT STUDIES IN SEVERE CHRONIC LEFT HEART FAILURE ARRHYTHMIAS AND OXYGEN DESATURATION

Overnight studies were performed in 10 patients with severe chronic left heart failure (New York Heart Association grades III and IV) without pulmonary disease and in eight controls. Transcutaneous oxygen (Po2) and carbon dioxide tensions (Pco2) and oxygen saturation were measured and the electro-cardiogram was recorded. During sleep mean oxygen saturation fell to 92.7% (minimum 86.1%) from 95.1% when awake. During the night oxygen saturation was below 95% for 62% of the time, below 90% for 6% of the time, and below 85% for 1% of the time. In four patients there were oxygen desaturation dips (a fall of greater than 4% in oxygen saturation from a stable baseline that lasted greater than 30 s) with concurrent increases in Pco2. Two patients had bradycardia during the dips: in one there was non-sustained ventricular tachycardia during the dips and in the other there was ST depression (greater than 0.1 mV at 80 ms after the J point) during a dip. In the controls the fall in mean oxygen saturation from 95.4% when they were awake to 94.4% when they were asleep was less than the fall in patients with heart failure and there were no desaturation dips or arrhythmias. Thus patients with severe heart failure had episodes of oxygen desaturation during sleep, some of which were associated with arrhythmia. Such episodes may be related to the increased risk of sudden death in chronic heart failure.

Transcatheter Aortic Valve Implantation in Degenerate Failing Aortic Homograft Root Replacements

To the Editor: As with all bioprosthetic aortic valve substitutes, homografts are prone to late degeneration characterized by dense calcification and valve dysfunction. Reoperation in patients with prior homograft aortic root replacement may carry a substantial risk, particularly in elderly

Short-stepping gait in severe heart failure

Background—Patients with severe chronic heart failure seem to take shorter steps than healthy controls when walking on a treadmill and when walking freely along a corridor. In healthy individuals the pattern of walking affects the oxygen cost of exercise, and so this observation might be relevant to the limitation of exercise in heart failure. Method—Length of stride was analysed as stride/stature index in 15 controls, 10 patients with moderate heart failure, 10 patients with severe heart failure, and 10 patients with angina, walking at a constant speed/stature index. Results—The stride/stature index was 0·64 in the controls in patients with New York Heart Association (NYHA) class II heart failure, and in patients with angina. It was 0·49 in patients with NYHA class III heart failure. In the patients with heart failure the stride/stature index correlated with exercise capacity determined as peak oxygen consumption Vo2max (R = +0·62, p < 0·005). When healthy controls walked in time to a metronome adjusted to decrease their stride/stature index to approximately that seen in severe heart failure steady-state oxygen consumption increased by a mean of 15%. Conclusions—The length of stride is reduced in severe heart failure, and when healthy controls adopt this gait the oxygen cost of walking is increased. A short-stepping gait may contribute to the limitation of exercise capacity in heart failure.

Changes in pulmonary microvascular permeability accompanying re-expansion oedema: evidence from dual isotope scintigraphy.

The pathophysiological mechanism of pulmonary oedema following rapid re-expansion of a collapsed lung is poorly understood. It has been suggested that the period of collapse or subsequent reinflation produces an increase in pulmonary microvascular permeability. To investigate this, the pulmonary accumulation of the plasma protein transferrin was measured by radiolabelling it in vivo with indium-113m. Plasma protein accumulation was calculated after correcting the accumulation of transferrin for changes in intrathoracic blood distribution by simultaneously monitoring technetium-99m labelled red blood cells. Functional images of plasma protein accumulation were constructed for the lung fields on a pixel by pixel basis. Investigations were performed on 14 subjects after drainage of a pleural effusion (n = 9) or evacuation of a pneumothorax (n = 5), and on 11 control subjects. Plasma protein accumulation was greater over the regions of lung re-expansion (-0.1-9.6, mean 2.9 x 10(-3)/min) than over the corresponding region of the contralateral lung (-1.2-0.8, mean 0.01 x 10(-3)/min; p less than 0.001). Patients who had undergone re-expansion procedures also had significantly greater plasma protein accumulation than normal controls. Nine of the 14 patients in the re-expansion group had clearly identifiable areas of increased plasma protein accumulation that corresponded to the part of the lung that had been re-expanded; no regional abnormalities were recorded in the control group. These results suggest that the reinflated lung displays abnormal microvascular permeability.

Combined coronary and perfusion cardiovascular magnetic resonance for the assessment of coronary artery stenosis.

The purpose of this study was to evaluate the feasibility and accuracy of combined coronary and perfusion cardiovascular magnetic resonance (CMR) in the assessment of coronary artery stenosis. Thirty-five consecutive patients (27 men, eight women, age range 34-81 years), undergoing cardiac catheterization, were assessed with 3D coronary CMR and rest-stress perfusion CMR. Significant coronary stenosis was determined by vessel narrowing or signal loss with coronary CMR, and by abnormal contrast enhancement with perfusion CMR. Coronary artery diameter stenosis greater than 50% was considered significant with conventional cardiac catheterization. Seventeen patients had significant coronary artery disease, and in these there were 35 significant stenoses on cardiac catheterization. All left main stem arteries were normal on both cardiac catheterization and coronary CMR. For the diagnosis of coronary artery stenosis, coronary CMR had a sensitivity of 92% for the left anterior descending artery (LAD), 79% for the right coronary artery (RCA), but only 13% for the circumflex coronary artery (LCX). Perfusion CMR had corresponding sensitivities of 69%, 86%, and 63%, respectively. For all arteries the accuracies for coronary and perfusion CMR were 67% and 72%, respectively. Combining coronary and perfusion CMR improved the accuracy to 77%. These data demonstrate that in patients with suspected coronary artery disease, combined coronary and perfusion CMR is feasible, increases the accuracy of detection of significant coronary stenosis, and offers the possibility of combined anatomical and hemodynamic assessment of coronary artery stenosis.

Evaluation of free-breathing three-dimensional magnetic resonance coronary angiography with hybrid ordered phase encoding (HOPE) for the detection of proximal coronary artery stenosis.

We evaluated free‐breathing, prospective navigator‐gated, three‐dimensional (3D) magnetic resonance coronary angiography (MRCA) with hybrid ordered phase‐encoding (HOPE), in the detection of proximal coronary artery stenosis. The coronary arteries were imaged in 46 patients undergoing cardiac catheterization. The mean scan time was 48 minutes. The mean arterial length (mm) visualized was left main stem (LMS) 11.7 (SD 4.5), left anterior descending (LAD) 30.1 (SD 11.1), circumflex (LCx) 15.5 (SD 8.6), and right (RCA) 56.2 (SD 20.8). Twenty‐three patients had coronary artery disease with 47 significant stenoses on cardiac catheterization. All LMS were normal on both catheterization and MRCA. MRCA sensitivity was highest for the LAD (89% CI 65%–99%) and RCA (76% CI 50%–93%), but lower for the LCx (50% CI 21%–79%). Specificity ranged from 72%–100%. Improvements in image quality, length of vessel seen, and specific imaging of the LCx are required for MRCA to become an alternative to cardiac catheterization. J. Magn. Reson. Imaging 2001;14:677–684.