Claire E. Raphael

Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure

Background: Two ways to evaluate the symptoms of heart failure are the New York Heart Association (NYHA) classification and asking patients how far they can walk (walk distance). The NYHA system is commonly used, although it is not clear how individual clinicians apply it. Aim: To investigate how useful these measures are to assess heart failure and whether other questions might be more helpful. Methods: 30 cardiologists were asked what questions they used when assessing patients with heart failure. To assess interoperator variability, two cardiologists assessed a series of 50 patients in classes II and III using the NYHA classification. 45 patients who had undergone cardiopulmonary testing were interviewed using a specially formulated questionnaire. They were also asked how far they could walk before being stopped by symptoms, and then tested on their ability to estimate distance. Results: The survey of cardiologists showed no consistent method for assessing NYHA class and a literature survey showed that 99% of research papers do not reference or describe their methods for assigning NYHA classes. The interoperator variability study showed only 54% concordance between the two cardiologists. 70% of cardiologists asked patients for their walk distance; however, this walk distance correlated poorly with actual exercise capacity measured by cardiopulmonary testing (ρ = 0.04, p = 0.82). Conclusion: No consistent method of assessing NYHA class is in use and the interoperator study on class II and class III patients gave a result little better than chance. Some potential questions are offered for use in assessment. Walking distance, although frequently asked, does not correlate with formally measured exercise capacity, even after correction for patient perception of distance, and has never been found to have prognostic relevance. Its value is therefore doubtful.

Quantifying the paradoxical effect of higher systolic blood pressure on mortality in chronic heart failure

Background: Although higher blood pressures are generally recognised to be an adverse prognostic marker in risk assessment of cardiology patients, its relationship to risk in chronic heart failure (CHF) may be different. Objective: To examine systematically published reports on the relationship between blood pressure and mortality in CHF. Methods: Medline and Embase were used to identify studies that gave a hazard or relative risk ratio for systolic blood pressure in a stable population with CHF. Included studies were analysed to obtain a unified hazard ratio and quantify the degree of confidence. Results: 10 studies met the inclusion criteria, giving a total population of 8088, with 29 222 person-years of follow-up. All studies showed that a higher systolic blood pressure (SBP) was a favourable prognostic marker in CHF, in contrast to the general population where it is an indicator of poorer prognosis. The decrease in mortality rates associated with a 10 mm Hg higher SBP was 13.0% (95% CI 10.6% to 15.4%) in the heart failure population. This was not related to aetiology, ACE inhibitor or β blocker use. Conclusion: SBP is an easily measured, continuous variable that has a remarkably consistent relationship with mortality within the CHF population. The potential of this simple variable in outpatient assessment of patients with CHF should not be neglected. One possible application of this information is in the optimisation of cardiac resynchronisation devices.

Implantable Cardioverter-Defibrillator Recipient Attitudes towards Device Deactivation: How Much do Patients Want to Know?

Background:  Patients receiving implantable cardioverter‐defibrillators (ICDs) often have severely impaired left ventricular function and a poor prognosis. Having an ICD in situ effectively denies them the possibility of a quick, arrhythmic death. It is still unclear if and when the end of life and device deactivation should be discussed with patients and how much patients want to know prior to ICD implantation.

Defining the genetic architecture of hypertrophic cardiomyopathy: re-evaluating the role of non-sarcomeric genes

Abstract Aim Hypertrophic cardiomyopathy (HCM) exhibits genetic heterogeneity that is dominated by variation in eight sarcomeric genes. Genetic variation in a large number of non-sarcomeric genes has also been implicated in HCM but not formally assessed. Here we used very large case and control cohorts to determine the extent to which variation in non-sarcomeric genes contributes to HCM. Methods and results We sequenced known and putative HCM genes in a new large prospective HCM cohort (n = 804) and analysed data alongside the largest published series of clinically genotyped HCM patients (n = 6179), previously published HCM cohorts and reference population samples from the exome aggregation consortium (ExAC, n = 60 706) to assess variation in 31 genes implicated in HCM. We found no significant excess of rare (minor allele frequency < 1:10 000 in ExAC) protein-altering variants over controls for most genes tested and conclude that novel variants in these genes are rarely interpretable, even for genes with previous evidence of co-segregation (e.g. ACTN2). To provide an aid for variant interpretation, we integrated HCM gene sequence data with aggregated pedigree and functional data and suggest a means of assessing gene pathogenicity in HCM using this evidence. Conclusion We show that genetic variation in the majority of non-sarcomeric genes implicated in HCM is not associated with the condition, reinforce the fact that the sarcomeric gene variation is the primary cause of HCM known to date and underscore that the aetiology of HCM is unknown in the majority of patients.

The rise, fall, and possible resurrection of renal denervation

Renal denervation has a chequered history. Dramatic reductions in blood pressure after denervation of the renal arteries were observed in early trials, but later trials in which denervation was tested against a sham procedure produced neutral results. Although a sound pathophysiological basis exists for interruption of the renal sympathetic nervous system as a treatment for hypertension, trial data to date are insufficient to support renal denervation as an established clinical therapy. In this Perspectives article, we summarize the currently available trial data, device development, and trials in progress, and provide recommendations for future trial design.

Tuberculous constrictive pericarditis

Introduction: Constrictive pericarditis is characterized by constriction of the heart secondary to pericardial inflammation. Cardiovascular magnetic resonance (CMR) imaging is useful imaging modality for addressing the challenges of confirming this diagnosis. It can be used to exclude other causes of right heart failure, such as pulmonary hypertension or myocardial infarction, determine whether the pericardium is causing constriction and differentiate it from restrictive cardiomyopathy, which also causes impaired cardiac filling. Case Presentation: A 77-year-old man from a country with high incidence of tuberculosis presented with severe dyspnea. Echocardiography revealed a small left ventricle with normal systolic and mildly impaired diastolic function. Left heart catheterization revealed non-obstructive coronary disease, not felt contributory to the dyspnea. Anatomy imaging with cardiovascular magnetic resonance imaging (CMR) showed global, severely thickened pericardium. Short tau inversion recovery (STIR) sequences for detection of oedema/ inflammation showed increased signal intensity and free breathing sequences confirmed septal flattening on inspiration. Late gadolinium imaging confirmed enhancement in the pericardium, with all findings suggestive of pericardial inflammation and constriction. Conclusions: CMRwith STIRsequences, free breathing sequences and late gadolinium imaging can prove extremely useful for diagnosing constrictive pericarditis.

Atypical case of post-partum cardiomyopathy: an overlap syndrome with arrhythmogenic right ventricular cardiomyopathy?

A middle-aged female patient presented with increasing dyspnoea following delivery of her second child. Echocardiography showed left ventricular (LV) dilatation and severe global impairment of systolic function (ejection fraction < 10%) but normal right ventricular (RV) dimensions. Plasma B-type natriuretic peptide level was elevated. Post-partum cardiomyopathy (PPCM) was considered and after initiating appropriate heart failure pharmacotherapy, her symptoms improved significantly. Cardiovascular MR showed RV free wall dyskinesia and aneurysms at the LV apex, RV free wall and RV outflow tract. Genetic analysis showed a C11842T substitution in the titin gene (TTN). This is the first case to propose an overlap syndrome of PPCM and arrhythmogenic RV cardiomyopathy.

93 Ejection Fraction by Cardiovascular Magnetic Resonance Predicts Adverse Outcomes Post Aortic Valve Replacement

Introduction Predicting prognosis following aortic valve replacement (AVR) in patients with aortic stenosis (AS) remains challenging. Current guidelines recommend that surgery should be offered when ejection fraction (EF) is <50%. We sought to investigate the prognostic significance of EF calculated by cardiovascular magnetic resonance (CMR) in the long term survival of patients following AVR. Methods 80 patients (69 ± 11 years old at time of surgery; 55 male) scheduled for AVR underwent CMR assessment. 52 patients had severe AS (area <1cm2), 28 patients had moderate AS (area 1.0–1.5cm2) and other qualifying reasons for AVR. 44 patients had additional coronary artery disease.Patients were categorised into three groups according to EF prior to surgery: Group 1 (EF <50%; n = 26), Group 2 (EF of 50–70%; n = 26) and Group 3 (EF >70%; n = 28). A median 5.0 ± 1.8 years follow-up was completed using the National Strategic Tracing Scheme and hospital notes. Results Univariate analysis of all cause mortality using the Kaplan-Meier estimator demonstrated significantly higher mortality in patients with Group 1 (EF <50%) compared to those in group 3 (EF >70%; .03).There was no statistical difference between group 2 (EF of 50–70%) and the remaining 2 groups. Abstract 93 Figure 1 Kaplan-Meier survival curve of all cause mortality in Group 1 (EF <50%), Group 2 (EF 50–70%) and Group 3 (EF >70%) Conclusion Pre-operative EF is a significant predictor of mortality following AVR. Patients with EF <50% have the worst prognosis whereas those with EF >70% have the best prognosis. We aim to incease the sample size to determine whether a progressive decrease in EF per se even when above 50% should initiate consideration for AVR.

Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy: Insights From Wave Intensity Analysis and Magnetic Resonance

Background Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. Objectives Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. Methods Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. Results Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). Conclusions Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment.

Quantification of Survival Gain From Cardiac Resynchronization Therapy: Nonlinear Growth With Time, and Greater Gain in Low-Risk Patients, Make Raw Trial Data an Underestimate of Real-World Behavior

Objectives The goal of this study was to examine the impact of calculation-window duration on lifespan gain (as observed in trials) and on who gains most. Background The landmark trials of biventricular pacing (cardiac resynchronization therapy [CRT]) typically ran for <1 device battery life, and they may therefore underestimate lifespan benefit over longer durations. Methods We conducted a meta-analysis of biventricular pacing trials to calculate lifespan gained: first, within the duration of randomized controlled trial data up to 2 years; second, over a 5-year typical battery life; and third, over >1 battery life. Importantly, we applied the Gompertz method for age-related increase in mortality from non–CRT-preventable causes. Results Five landmark trials (COMPANION [Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure], CARE-HF (CArdiac REsynchronization–Heart Failure), MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT (Resynchronization–Defibrillation for Ambulatory Heart Failure)) provided data for 2 years (6,561 patients), with an average hazard ratio of 0.71. Lifespan gained across all trials increased nonlinearly with time from 0.1 month at 1 year, to 0.5 month at 2 years, and a projected 6.5 months at 5 years (65 times more than at 1 year). After multiple devices, it reached 14 months, involving on average 1.6 devices (i.e., 8.8 months per device implanted). Moreover, while over a short window (e.g., 2 years), lower-mortality patients may gain less than higher-mortality patients (1.4 vs. 2.3 months), their positions reverse by 15 years (16.0 vs. 13.7 months). Conclusions Lifespan gain from biventricular pacing rises nonlinearly with time. Early on, higher-risk patients exhibit more gain, but later, lower-risk patients exhibit more gain. Quantifying gain over less than a patient’s lifetime underestimates lifespan gain. Over the first 1 or 2 years, lower-risk patients may seem to gain less, although they may ultimately be the ones who gain the most.