Episodic circulatory collapse caused by intermittent prosthetic aortic valve dysfunction.

An 80-year-old woman with a 20-mm Medtronic Hall (tilting-disc) aortic prosthesis presented with episodes of chest pain associated with circulatory collapse and subsequent rapid spontaneous recovery. A computed tomography angiogram demonstrated no evidence of aortic dissection, pulmonary embolus, or coronary artery disease. A transthoracic echocardiogram demonstrated a well-functioning prosthetic aortic valve. After another inpatient episode, auscultation demonstrated an intermittent absence of the prosthetic second heart sound. A transesophageal echocardiography examination revealed that the aortic valve was intermittently sticking in the open position. During the emergency replacement, the existing valve was noted to have pannus and overlying thrombus, which are rare in this type of valve but can lead to dramatic circulatory collapse when present. This case demonstrates how a diagnosis of intermittent valve dysfunction can prove elusive. It is important, as part of the assessment of mechanical valves, to perform regular, careful auscultation and echocardiographic examination, with emphasis on recording in Doppler or M-mode through the valve at slow sweep speeds for a prolonged period in order to maximize the chance of diagnosing episodic valve dysfunction.

Increased atrial contribution to left ventricular filling compensates for impaired early filling during exercise in heart failure with preserved ejection fraction.

BACKGROUND: The role of left atrial (LA) function on exercise remains poorly understood in heart failure with preserved ejection fraction (HfpEF) despite its key role in optimizing left ventricular (LV) diastolic function. We used resting and exercise radionuclide ventriculography to investigate the role of LA function in the pathophysiology of HfpEF. METHODS AND RESULTS: A total of 25 patients with HfpEF and 15 age- and gender-matched controls were recruited. All subjects underwent resting echocardiogram, metabolic exercise testing to peak effort, and radionuclide ventriculography (at rest and exercise [to 35% of heart rate reserve]). At rest LA and LV function were similar in patients and controls. During exercise, HfpEF patients had lower left ventricular ejection fraction (69 +/- 9% vs. 73 +/- 10%, P < .05) and lower peak early filling rate (387 +/- 109 end-diastolic count/sec vs. 561 +/- 156 end-diastolic count/sec, P < .001). During exercise, the atrial contribution to LV filling was significantly higher in patients than controls (46 +/- 11% vs. 30 +/- 9%, P < .001). Atrial contribution to LV filling correlated negatively with peak early filling rate during exercise (r = -0.6, P < .001). Peak early filling rate correlated positively with peak oxygen consumption (r = 0.485, P = .004) and negatively with minute/carbon dioxide production (r = -0.423, P = .013). CONCLUSION: Patients with HfpEF have increased atrial contribution to LV filling as a compensatory response to impaired early LV filling during cycle exercise.

Left ventricular torsion and strain patterns in heart failure with normal ejection fraction are similar to age-related changes.

AIMS: We used speckle tracking echocardiography (STE) to make a comparison between the effects of ageing and of heart failure with normal ejection fraction (HfnEF) on left ventricular (LV) torsion and strain patterns. METHODS AND RESULTS: Forty patients with HfnEF, 27 young controls and 26 older controls, were prospectively recruited. All subjects underwent clinical examination, 12-lead electrocardiogram, pulmonary function test, echocardiogram, and metabolic exercise test. LV torsion increases with advancing age (older controls vs. young controls, 2.2 +/- 0.9 vs. 1.4 +/- 0.8 degrees /cm; P = 0.03). Circumferential strain was enhanced in patients with HfnEF (-24.7 +/- 4.7 vs. -20.0 +/- 4.9%; P = 0.003). Rotational deformation delay (time difference between peak basal rotation and peak apical rotation), global circumferential strain, E-velocity deceleration time, and LV end-diastolic volume index were independent predictors of LV torsion. LV torsion and body mass index were independent predictors of LV untwist rate. CONCLUSION: Ageing is associated with increased LV torsion secondary to reduced rotational deformation delay and increased peak basal rotation. LV torsion and strain patterns in patients with HfnEF are similar to age-related changes apart from circumferential strain, which is enhanced in patients with HfnEF.

Reduced in vivo skeletal muscle oxygen consumption in patients with chronic heart failure--a study using Near Infrared Spectrophotometry (NIRS).

AIM: We used Near Infrared Spectrophotometry (NIRS) during arterial occlusion to measure resting skeletal muscle oxygen consumption in chronic heart failure (CHF) patients and in age-matched healthy volunteers (HVs). METHODS: Fifteen CHF patients (ten males) and eleven HVs (six males) had echocardiographic evaluation followed by measurement of the oxygen consumption of the brachioradialis muscle using NIRS. This involved continuous measurement of the oxygenated haemoglobin concentration ([Oxy-Hb]) and deoxy-haemoglobin concentration ([Deoxy-Hb]) with an Oxiplex TS NIRS probe first under basal overnight fasted resting conditions followed by 1 min of forearm arterial occlusion. A linear decline was observed in [Oxy-Hb-Deoxy-Hb] during the arterial occlusion and the oxygen consumption rate was calculated from the initial slope observed. RESULTS: CHF patients were 59+/-2.8 years old with Left Ventricular Ejection Fraction (LVEF) 31%+/-2.2 and the HVs were 52+/-4.8 years old with LVEF 62%+/-2.5. The resting muscle oxygen consumption rate was significantly reduced in CHF patients versus HVs (0.04+/-0.01 mlO(2)/min/100 g versus 0.07+/-0.01 mlO(2)/min/100 g) p<0.005. CONCLUSIONS: There is a significant reduction in resting oxygen consumption per gram of tissue in skeletal muscle of patients with CHF.

Insights into how to conduct a clinical trial in the UK.

New researchers may find starting and conducting clinical studies in the UK complicated and time-consuming. In this article, we describe our collective experiences and provide some pointers on how to navigate through the various committees and regulatory bodies. The article is intended to aid junior researchers in understanding the study process and to provide them with some insight on how to get through this complex system successfully.

Rivaroxaban in patients with a recent acute coronary syndrome event: integration of trial findings into clinical practice.

Despite significant advances in the management of acute coronary syndrome (ACS) and long-term antiplatelet therapy after an ACS event, patients continue to be at risk of further cardiovascular events. There is evidence that recurrent events are at least partly attributed to the persistent activation of the coagulation system after ACS. Various anticoagulants, including vitamin K antagonists (VKAs) and non-VKA oral anticoagulants, have been evaluated in patients post-ACS, in combination with antiplatelet therapy. The desired outcome would be a further reduction of recurrent cardiovascular events with low or acceptable levels of bleeding complications. Here, we provide an overview of the current clinical trial data of non-VKA oral anticoagulants, focusing on rivaroxaban in particular, for secondary prevention in patients with a recent ACS event.

The pathophysiology of heart failure with preserved ejection fraction: from molecular mechanisms to exercise haemodynamics.

The pathophysiology of HfpEF is complex. In this review we discuss the molecular aspects of HfpEF as well as the profoundly disturbed haemodynamics with particular focus on exercise haemodynamic abnormalities.

Abnormal left ventricular torsion and cardiac autonomic dysfunction in subjects with type 1 diabetes mellitus.

Left ventricular torsion is increased and cardiac energetics are reduced in uncomplicated type 1 diabetes mellitus (T1DM). Our aim was to determine the relationships of these abnormalities to cardiovascular autonomic neuropathy (CAN) in subjects with T1DM. A cross-sectional study was conducted in 20 subjects with T1DM free of known coronary heart disease attending an outpatient clinic. Cardiovascular autonomic neuropathy was assessed using heart rate variability studies and the continuous wavelet transform method. Left ventricular function was determined by speckle tracking echocardiography. Magnetic resonance spectroscopy and stress magnetic resonance imaging were used to measure cardiac energetics and myocardial perfusion reserve index, respectively. Twenty subjects (age, 35 ± 8 years; diabetes duration, 16 ± 9 years; hemoglobin A(1c), 8.0% ± 1.1%) were recruited. Forty percent of the subjects exhibited definite or borderline CAN. Log peak radial strain was significantly increased in subjects with CAN compared with those without (1.56 ± 0.06 vs 1.43 ± 0.14, respectively; P = .011). Data were adjusted for log duration of diabetes, and log left ventricular torsion correlated (r = 0.593, P = .01) with log low-frequency to high-frequency ratio during the Valsalva maneuver. Log isovolumic relaxation time correlated significantly with log Valsalva ratio and log proportion of differences in consecutive RR intervals of normal beats greater than 50 milliseconds during deep breathing. However, CAN did not correlate with cardiac energetics or myocardial perfusion reserve index. Spectral analysis of low-frequency to high-frequency ratio power during the Valsalva maneuver is associated with altered left ventricular torsion in subjects with T1DM. Parasympathetic dysfunction is closely associated with diastolic deficits. Cardiovascular autonomic neuropathy is not however the principal cause of impaired cardiac energetics. The role of CAN in the development of cardiomyopathy warrants further evaluation.

Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction.

BACKGROUND: This study assessed the chronotropic response to exercise and heart rate (HR) recovery after exercise in a carefully phenotyped group of patients with heart failure with preserved left ventricular ejection fraction (HfpEF) and a control group of similar age and gender distribution. METHODS AND RESULTS: We studied 41 patients with HfpEF, 41 healthy controls, and 16 hypertensive controls. None were taking HR-limiting medications. All study participants had clinical examination, 12-lead ECG, pulmonary function test, echocardiogram, and metabolic exercise test with HR monitoring throughout exercise. Chronotropic response was measured by the percentage of the HR reserve used during maximal exercise and the peak exercise HR as a percentage of predicted maximal HR. Patients with HfpEF were generally women (70%), overweight, aged 69+/-8 years. Controls were of similar gender (63%) and age (67+/-6 years). Patients with HfpEF had significantly reduced peak VO(2) compared with controls (20+/-4 mL kg(-1) min(-1) versus 31+/-6 mL kg(-1) min(-1), P<0.001) and greater minute ventilation-carbon dioxide production relationship (V(E)/V(CO2)) slope) (33+/-6 versus 29+/-4, P<0.001). Chronotropic incompetence was significantly more common in patients with HfpEF compared with matched healthy controls as measured by the percentage of the HR reserve used during maximal exercise (63% versus 2%, <0.001) and percentage of predicted maximal HR (34% versus 2%, <0.001). In addition, abnormal HR recovery 1-minute after exercise (defined as the reduction in the HR from peak exercise 1-minute after exercise) was also significantly more common in patients with HfpEF compared with controls (23% versus 2%, P=0.01). Hypertensive controls showed similar chronotropic response to peak exercise and HR recovery after exercise as healthy controls. CONCLUSIONS: Patients with HfpEF have impaired chronotropic incompetence during maximal exercise and abnormal HR recovery after exercise.

Myocardial contractile inefficiency and dyssynchrony in heart failure with preserved ejection fraction and narrow QRS complex.

BACKGROUND: Using speckle-tracking imaging (STI), the aims of this study were to assess dyssynchrony and quantify the myocardial energy wasted by contractility in delayed segments by determining the longitudinal strain delay index (LSDi) in patients with heart failure with preserved ejection fraction (HFpEF). METHOD: Thirty-eight patients with HFpEF and 33 matched controls were recruited. All subjects underwent clinical examinations, 12-lead electrocardiography, pulmonary function tests, echocardiography, and metabolic exercise tests. LSDi was determined, the magnitude of which is a measure of the amount of wasted energy. Global and segmental systolic and diastolic dyssynchrony was assessed by STI. RESULTS: LSDi was significantly higher in patients with HFpEF than controls (-14.36 +/- 8.24% vs -10.73 +/- 5.62%, P < .05). Patients with HFpEF exhibited left ventricular (LV) systolic and diastolic dyssynchrony, with the LV anterior wall displaying the most delayed motion. CONCLUSION: Patients with HFpEF exhibited increased myocardial contractile inefficiency. They also exhibited LV systolic and diastolic dyssynchrony, with the LV anterior wall displaying the most delayed motion.

(31)P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy: Experiences at 3T.

BACKGROUND: (31)P magnetic resonance spectroscopy (MRS) allows measurement of in vivo high-energy phosphate kinetics in the myocardium. While traditionally (31)P cardiac spectroscopy is performed at 1.5T, cardiac MRS at higher field strength can theoretically increase signal to noise ratio (SNR) and spectral resolution therefore improving sensitivity and specificity of the cardiac spectra. The reproducibility and feasibility of performing cardiac spectroscopy at 3T is presented here in this study in healthy volunteers and patients with hypertrophic cardiomyopathy. METHODS: Cardiac spectroscopy was performed using a Phillips 3T Achieva scanner in 37 healthy volunteers and 26 patients with hypertrophic cardiomyopathy (HCM) to test the feasibility of the protocol. To test the reproducibility a single volunteer was scanned eight times on separate occasions. A single voxel (31)P MRS was performed using Image Selected In vivo Spectroscopy (ISIS) volume localization. RESULTS: The mean phosphocreatine/adenosine triphosphate (PCr/ATP) ratio of the eight measurements performed on one individual was 2.11+/-0.25. Bland Altman plots showed a variance of 12% in the measurement of PCr/ATP ratios. The PCr/ATP ratio was significantly reduced in HCM patients compared to controls, 1.42+/-0.51 and 2.11+/-0.57, respectively, P<0.0001. (All results are expressed as mean+/-standard deviation). CONCLUSIONS: Here we demonstrate that cardiac (31)P MRS at 3T is a reliable method of measuring in vivo high-energy phosphate kinetics in the myocardium for clinical studies and diagnostics. Based on our data an impairment of cardiac energetic state in patients with hypertrophic cardiomyopathy is indisputable.

Increased left ventricular torsion in uncomplicated type 1 diabetic patients: the role of coronary microvascular function.

OBJECTIVE: We used speckle tracking echocardiography to study the early changes in left ventricular (LV) torsion in young patients with uncomplicated type 1 diabetes and stress magnetic resonance imaging (MRI) to assess its interrelationships with coronary microangiopathy. RESEARCH DESIGN AND METHODS: We recruited 33 asymptomatic subjects with type 1 diabetes and 32 age-matched healthy control subjects. All subjects underwent echocardiograms. Stress MRIs were performed in 30 subjects (8 healthy control subjects) to compute myocardial perfusion reserve index (MPRI). RESULTS: A significant increase in LV torsion (2 +/- 0.7 vs. 1.4 +/- 0.7 degrees /cm, P < 0.05) was identified in longer-term and retinopathy-positive type 1 diabetic subjects (1.9 +/- 0.7 vs. 1.4 +/- 0.7 degrees /cm, P < 0.05) as compared with the healthy control subjects. The MPRI was independently associated with increased LV torsion. CONCLUSIONS: We demonstrate that LV torsion is increased in young patients with uncomplicated type 1 diabetes and that coronary microvascular disease may play a key pathophysiological role in the development of increased LV torsion.

Multi-centre experience on the use of perhexiline in chronic heart failure and refractory angina: old drug, new hope.

AIMS: The objective of this study is to report on our 5-year collective experience on the use of perhexiline in the UK, in patients with chronic heart failure (CHF) and/or refractory angina with respect to 'real-life' drug side effects and toxicity, therapeutic drug level monitoring, 5 year mortality outcomes and predictors of response to perhexiline therapy. METHODS AND RESULTS: Data on clinical history, perhexiline monitoring, follow-up, and mortality were retrospectively collated from centralized perhexiline databases from two tertiary referral centres. A total of 151 patients were on perhexiline therapy at two UK tertiary referral centres. At 3-4 months, 68.8% of patients had drug level within the therapeutic range and 20.8% were above the therapeutic range. A total of 58.9% of patients reported to have felt better on the perhexiline (responders). The presence of refractory angina was an independent predictor of response to perhexiline therapy (odds ratio 2.84, 95% confidence interval 1.28-6.32, P = 0.01). Five-year mortality was non-significantly different between patients with refractory angina, CHF, or both (20.5, 31.0, and 38.4%, P = 0.20, respectively). CONCLUSION: Perhexiline therapy provides symptomatic relief in the majority of patients with minimal side effects or toxicity. Careful therapeutic level monitoring for dose titration is important to prevent acute and chronic toxicity. Patients with refractory angina were more likely to be responders.