ChaMP-CMD: A Phenotype-Blinded, Randomized Controlled, Cross-Over Trial.

BACKGROUND: Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy. METHODS: Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). RESULTS: Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; P<0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; P=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; P=0.549). CONCLUSIONS: Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.

Invasive and non-invasive assessment of ischaemia in chronic coronary syndromes: translating pathophysiology to clinical practice.

Intracoronary physiology testing has emerged as a valuable diagnostic approach in the management of patients with chronic coronary syndrome, circumventing limitations like inferring coronary function from anatomical assessment and low spatial resolution associated with angiography or non-invasive tests. The value of hyperaemic translesional pressure ratios to estimate the functional relevance of coronary stenoses is supported by a wealth of prognostic data. The continuing drive to further simplify this approach led to the development of non-hyperaemic pressure-based indices. Recent attention has focussed on estimating physiology without even measuring coronary pressure. However, the reduction in procedural time and ease of accessibility afforded by these simplifications needs to be counterbalanced against the increasing burden of physiological assumptions, which may impact on the ability to reliably identify an ischaemic substrate, the ultimate goal during catheter laboratory assessment. In that regard, measurement of both coronary pressure and flow enables comprehensive physiological evaluation of both epicardial and microcirculatory components of the vasculature, although widespread adoption has been hampered by perceived technical complexity and, in general, an underappreciation of the role of the microvasculature. In parallel, entirely non-invasive tools have matured, with the utilization of various techniques including computational fluid dynamic and quantitative perfusion analysis. This review article appraises the strengths and limitations for each test in investigating myocardial ischaemia and discusses a comprehensive algorithm that could be used to obtain a diagnosis in all patients with angina scheduled for coronary angiography, including those who are not found to have obstructive epicardial coronary disease.

Impact of COVID-19 pandemic on the management of nonculprit lesions in patients presenting with ST-elevation myocardial infarction: Outcomes from the pan-London heart attack centers.

BACKGROUND: The impact of COVID-19 on the diagnosis and management of nonculprit lesions remains unclear. OBJECTIVES: This study sought to evaluate the management and outcomes of patients with nonculprit lesions during the COVID-19 pandemic. METHODS: We conducted a retrospective observational analysis of consecutive primary percutaneous coronary intervention (PPCI) pathway activations across the heart attack center network in London, UK. Data from the study period in 2020 were compared with prepandemic data in 2019. The primary outcome was the rate of nonculprit lesion percutaneous coronary intervention (PCI) and secondary outcomes included major adverse cardiovascular events. RESULTS: A total of 788 patients undergoing PPCI were identified, 209 (60%) in 2020 cohort and 263 (60%) in 2019 cohort had nonculprit lesions (p = .89). There was less functional assessment of the significance of nonculprit lesions in the 2020 cohort compared to 2019 cohort; in 8% 2020 cohort versus 15% 2019 cohort (p = .01). There was no difference in rates of PCI for nonculprit disease in the 2019 and 2020 cohorts (31% vs 30%, p = .11). Patients in 2020 cohort underwent nonculprit lesion PCI sooner than the 2019 cohort (p < .001). At 6 months there was higher rates of unplanned revascularization (4% vs. 2%, p = .05) and repeat myocardial infarction (4% vs. 1%, p = .02) in the 2019 cohort compared to 2020 cohort. CONCLUSION: Changes to clinical practice during the COVID-19 pandemic were associated with reduced rates of unplanned revascularization and myocardial infarction at 6-months follow-up, and despite the pandemic, there was no difference in mortality, suggesting that it is not only safe but maybe more efficacious.

Buddy-wire technique during rotational Atherectomy: Simple and effective solution to achieve strong back-up support.

A 52-year-old male underwent percutaneous coronary intervention (PCI) using rotational atherectomy (RA: 1.5-mm burr) for a severely calcified lesion in the proximal to mid obtuse marginal (OM) branch. Even with 7 Fr extra back-up guiding catheter via femoral access, the burr could not cross the lesion due to insufficient back-up support. In order to achieve stronger back-up support, we kept the burr at the position in the OM branch and placed a supportive wire in left anterior descending artery through the side of drive-shaft sheath of the Rotablator, which sufficiently stabilized the guiding catheter during the ablation and the burr crossed the lesion. This case demonstrates that a simple technique of placing additional supportive wire in the other vessel during RA could be an effective and safe solution to facilitate improved back-up support without necessity to change the PCI system used already.

Anatomic and procedural associations of transcatheter heart valve displacement following Evolut R implantation.

OBJECTIVES: This study aimed to predict the displacement of self-expanding transcatheter heart valves (THV) during final deployment. BACKGROUND: Accurate device positioning during transcatheter aortic valve implantation (TAVI) is crucial for optimal results. METHODS: At our institution, 103 patients who underwent transfemoral TAVI with Evolut R were retrospectively identified. Multiple linear regression models were created, and a predictor equation was built to quantify the factors that may affect THV behavior. RESULTS: Multiple linear regression analysis for THV displacement on the left coronary cusp (LCC) identified the angle between the THV and the ascending aorta (ATA), predilation, and less operator experience as independent predictors of upward displacement, whereas estimated glomerular filtration rate (eGFR) was inversely related with THV behavior (95% confidence interval: 0.219 to 0.340, 0.447 to 2.092, 0.165 to 1.757, and -0.053 to -0.011, respectively). Predictors of THV displacement on the noncoronary cusp side could not be identified using this model. CONCLUSIONS: The ATA at the point of recapture, predilation, and less operator experience were independent predictors of upward displacement of THV on the LCC side. eGFR was an independent predictor of THV downward displacement on the LCC side. Of them, the ATA was the strongest predictor. Physicians may need to adjust this angle adequately before deployment to achieve the appropriate position.

Long-term follow-up of covered stent implantation for various coronary artery diseases.

OBJECTIVES: The aims of this study were to evaluate the long-term clinical outcomes after coronary covered stent (CS) implantation and to compare the results according to the indications. BACKGROUND: To date, data on the long-term follow-up of coronary CS are limited, and no studies have been conducted to compare outcomes on the basis of specific lesions treated. METHODS: A total of 190 consecutive patients (212 lesions) implanted with CS and surviving until discharge between May 1997 and February 2017 were enrolled in this retrospective study. Clinical outcomes were evaluated and compared using the Gehan-Breslow-Wilcoxon test. RESULTS: CS was mainly used for the treatment of a saphenous vein graft (SVG) (51.4%), followed by coronary artery perforation (CAP) (25.0%) and coronary artery aneurysm (CAA) (11.8%). The median follow-up duration was 6.0 (interquartile range: 1.6-13.5) years. Target vessel myocardial infarction (MI), target vessel occlusion, target lesion revascularization, and stent thrombosis, frequently occurred in the early follow-up period (7.3%, 16.6%, 21.5%, and 8.9% at 1 year, respectively) and continued to increase throughout the long-term follow-up (14.8%, 38.6%, 38.7%, and 17.8% at 10 years, respectively). Target vessel occlusion, target vessel MI, and ST were not identified in CAA with superiority to CAP (Gehan-Breslow-Wilcoxon p-value = 0.010, 0.047, and 0.046, respectively). SVG had a higher rate of target vessel occlusion than CAA (p = 0.004). CONCLUSIONS: Clinical events after CS implantation frequently occurred in the early period and steadily increased in the long-term period. CS implantation in CAA was associated with fewer adverse cardiac events and may lead to safe and acceptable outcomes. However, CS implanted in CAP and SVG are associated with a high risk of long-term cardiac events.

Initial experience of a large, self-expanding, and fully recapturable transcatheter aortic valve: The UK & Ireland Implanters' registry.

OBJECTIVES: The UK & Ireland Implanters' registry is a multicenter registry which reports on real-world experience with novel transcatheter heart valves. BACKGROUND: The 34 mm Evolut R transcatheter aortic valve is a self-expanding and fully recapturable transcatheter aortic valve, designed to treat patients with a large aortic annulus. METHODS: Between January 2017 and April 2018, clinical, procedural and 30-day outcome data were prospectively collected from all patients receiving the 34 mm Evolut R valve across 17 participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2(VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 217 patients underwent attempted implant. Mean age was 79.5 ± 8.8 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.2% ± 3.4%. Iliofemoral access was used in 91.2% of patients. Device success was 79.7%. Mean gradient was 7.0 ± 4.6 mmHg and effective orifice area 2.0 ± 0.6 cm2 . Paravalvular regurgitation was more than mild in 7.2%. A new permanent pacemaker was implanted in 15.7%. Early safety was demonstrated in 91.2%. At 30 days, all-cause mortality was 3.2%, stroke 3.7%, and major vascular complication 2.3%. CONCLUSIONS: Real-world experience of the 34 mm Evolut R transcatheter aortic valve demonstrated acceptable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

Patent foramen ovale closure vs. medical therapy for cryptogenic stroke: a meta-analysis of randomized controlled trials.

Aims: The efficacy of patent foramen ovale (PFO) closure for cryptogenic stroke has been controversial. We undertook a meta-analysis of randomized controlled trials (RCTs) comparing device closure with medical therapy to prevent recurrent stroke for patients with PFO. Methods and results: We systematically identified all RCTs comparing device closure to medical therapy for cryptogenic stroke in patients with PFO. The primary efficacy endpoint was recurrent stroke, analysed on an intention-to-treat basis. The primary safety endpoint was new onset atrial fibrillation (AF). Five studies (3440 patients) were included. In all, 1829 patients were randomized to device closure and 1611 to medical therapy. Across all patients, PFO closure was superior to medical therapy for prevention of stroke [hazard ratio (HR) 0.32, 95% confidence interval (95% CI) 0.13-0.82; P = 0.018, I2 = 73.4%]. The risk of AF was significantly increased with device closure [risk ratio (RR) 4.68, 95% CI 2.19-10.00, P<0.001, heterogeneity I2 = 27.5%)]. In patients with large shunts, PFO closure was associated with a significant reduction in stroke (HR 0.33, 95% CI 0.16-0.72; P = 0.005), whilst there was no significant reduction in stroke in patients with a small shunt (HR 0.90, 95% CI 0.50-1.60; P = 0.712). There was no effect from the presence or absence of an atrial septal aneurysm on outcomes (P = 0.994). Conclusion: In selected patients with cryptogenic stroke, PFO closure is superior to medical therapy for the prevention of further stroke: this is particularly true for patients with moderate-to-large shunts. Guidelines should be updated to reflect this.

Intravenous Thrombolysis and Mechanical Thrombectomy in Patients with Stroke after TAVI: A Report of Two Cases.

Transcatheter Aortic Valve Implantation (TAVI) is an increasingly treatment modality for severe aortic stenosis, which is associated with a considerable peri-procedural risk of stroke. To date, the clinical safety and efficacy of Tissue plasminogen activator (tPA) and mechanical thrombectomy in stroke post-TAVI is not established. We describe 2 cases of patients with stroke after TAVI who received tPA therapy and mechanical thrombectomy.

Microcatheter knuckle technique: A novel technique for negotiating the subintimal space during chronic total occlusion recanalization.

OBJECTIVES: To establish if novel microcatheter knuckle technique (MKT) is feasible and efficacious in negotiating the subintimal space in difficult lesions during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: CTOs remain one of the most challenging lesion subsets in PCI. Guidewire manipulation and advancement of equipment within the subintimal space is sometimes challenging and aggressive manipulation in the subintimal space is feared, because of concern of vessel disruption and perforation. Here we introduce the MKT, for negotiating the subintimal space during challenging CTO PCI. METHODS: MKT is performed by creating a wire knuckle with polymer-jacketed guidewire and positioned in the subintimal space. Subsequently, a tapered-tip, kink-resistant microcatheter is advanced towards the knuckled tip of guidewire and the guidewire is simultaneously withdrawn; creating a knuckle-shaped microcatheter tip. The MKT was considered in CTO PCIs that involved subintimal techniques where resistance to guidewire knuckle advancement was encountered. Procedures were performed between March 2013 and June 2017 at our institution. RESULTS: During the study period, a total of 440 CTO PCIs were performed, from which seven were treated with MKT. MKT was successful in six patients and technical success was achieved in all seven patients. The MKT was successfully performed with both the antegrade and retrograde approach. CONCLUSION: We present a novel technique for negotiating the subintimal space in CTO PCI for cases where significant resistance is experienced restricting guidewire or material advancement in antegrade or retrograde dissection. The MKT appears to be efficacious complementing the CTO operator's armamentarium.

Comparison of ESC and NICE guidelines for patients with suspected coronary artery disease: evaluation of the pre-test probability risk scores in clinical practice.

The European Society of Cardiology (ESC) and UK National Institute for Health and Care Excellence (NICE) have recently published guidelines for investigating patients with suspected coronary artery disease (CAD). Both provide a risk score (RS) to assess the pre-test probability for CAD to guide clinicians to undertake the most effective investigation. The aim of the study was to establish whether there is a difference between the two RS models. We retrospectively reviewed records of 479 patients who presented to a UK district general hospital with chest pain between August 2011 and April 2013. The RS was calculated using ESC and NICE guidelines and compared. From the 479 patients, 277 (58%) were male and the mean age was 60 years. The mean RS was greater using NICE guidelines compared with ESC (66.3 vs 47.9%, 18.4% difference; p<0.0001). The difference in mean RS was smaller in patients with typical chest pain (13.0%). When we divided the cohort based on NICE criteria into 'high'- and 'low'-risk groups, the difference in the mean RS was 24.3% in the 'high'-risk group (p<0.001) compared with 2.8% in the 'low'-risk group. The UK NICE risk score model overestimates risk compared with the ESC model.

Transcatheter Aortic Valve Implantation to Treat Degenerated Aortic, Mitral and Tricuspid Bioprosthesis.

Transcatheter aortic valve implantation (TAVI) is now well established as the treatment of choice for patients with native aortic valve stenosis who are high or intermediate risk for surgical aortic valve replacement. Recent data has also supported the use of TAVI in patients at low surgical risk and also in anatomical subsets that were previously felt to be contra-indicated including bicuspid aortic valves and aortic regurgitation. With advancements and refinements in procedural techniques, the application of this technology has now been further expanded to include the management of degenerated bioprosthesis. After the demonstration of feasibility and safety in the management of degenerated aortic bioprosthetic valves, mitral and tricuspid bioprosthetic valve treatment is now also well-established and provides an attractive alternative to performing redo surgery. In this review, we appraise the latest clinical evidence and highlight procedural considerations when utilising TAVI technology in the management of degenerated aortic, mitral or tricuspid prosthesis.

Characterizing Mechanisms of Ischemia in Patients With Myocardial Bridges.

BACKGROUND: Myocardial bridges (MBs) are prevalent and can be associated with acute and chronic ischemic syndromes. We sought to determine the substrates for ischemia in patients with angina with nonobstructive coronary arteries and a MB in the left anterior descending artery. METHODS: Patients with angina with nonobstructive coronary arteries underwent the acquisition of intracoronary pressure and flow during rest, supine bicycle exercise, and adenosine infusion. Coronary wave intensity analysis was performed, with perfusion efficiency defined as accelerating wave energy/total wave energy (%). Epicardial endothelial dysfunction was defined as a reduction in epicardial vessel diameter ≥20% in response to intracoronary acetylcholine infusion. Patients with angina with nonobstructive coronary arteries and a MB were compared with 2 angina with nonobstructive coronary arteries groups with no MB: 1 with coronary microvascular disease (CMD: coronary flow reserve, <2.5) and 1 with normal coronary flow reserve (reference: coronary flow reserve, ≥2.5). RESULTS: Ninety-two patients were enrolled in the study (30 MB, 33 CMD, and 29 reference). Fractional flow reserve in these 3 groups was 0.86±0.05, 0.92±0.04, and 0.94±0.05; coronary flow reserve was 2.5±0.5, 2.0±0.3, and 3.2±0.6. Perfusion efficiency increased numerically during exercise in the reference group (65±9%-69±13%; P=0.063) but decreased in the CMD (68±10%-50±10%; P<0.001) and MB (66±9%-55±9%; P<0.001) groups. The reduction in perfusion efficiency had distinct causes: in CMD, this was driven by microcirculation-derived energy in early diastole, whereas in MB, this was driven by diminished accelerating wave energy, due to the upstream bridge, in early systole. Epicardial endothelial dysfunction was more common in the MB group (54% versus 29% reference and 38% CMD). Overall, 93% of patients with a MB had an identifiable ischemic substrate. CONCLUSIONS: MBs led to impaired coronary perfusion efficiency during exercise, which was due to diminished accelerating wave energy in early systole compared with the reference group. Additionally, there was a high prevalence of endothelial and microvascular dysfunction. These ischemic mechanisms may represent distinct treatment targets.

Rethinking False Positive Exercise Electrocardiographic Stress Tests by Assessing Coronary Microvascular Function.

BACKGROUND: Exercise electrocardiographic stress testing (EST) has historically been validated against the demonstration of obstructive coronary artery disease. However, myocardial ischemia can occur because of coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease. OBJECTIVES: The aim of this study was to assess the specificity of EST to detect an ischemic substrate against the reference standard of coronary endothelium-independent and endothelium-dependent microvascular function in patients with angina with nonobstructive coronary arteries (ANOCA). METHODS: Patients with ANOCA underwent invasive coronary physiological assessment using adenosine and acetylcholine. CMD was defined as impaired endothelium-independent and/or endothelium-dependent function. EST was performed using a standard Bruce treadmill protocol, with ischemia defined as the appearance of ≥0.1-mV ST-segment depression 80 ms from the J-point on electrocardiography. The study was powered to detect specificity of ≥91%. RESULTS: A total of 102 patients were enrolled (65% women, mean age 60 ± 8 years). Thirty-two patients developed ischemia (ischemic group) during EST, whereas 70 patients did not (nonischemic group); both groups were phenotypically similar. Ischemia during EST was 100% specific for CMD. Acetylcholine flow reserve was the strongest predictor of ischemia during exercise. Using endothelium-independent and endothelium-dependent microvascular dysfunction as the reference standard, the false positive rate of EST dropped to 0%. CONCLUSIONS: In patients with ANOCA, ischemia on EST was highly specific of an underlying ischemic substrate. These findings challenge the traditional belief that EST has a high false positive rate.

Complex percutaneous coronary intervention in patients unable to undergo coronary artery bypass grafting during the COVID-19 pandemic: insights from the UK-ReVasc Registry.

OBJECTIVES: Cardiac surgery for coronary artery disease was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with disease ordinarily treated with coronary artery bypass grafting (CABG) instead underwent percutaneous coronary intervention (PCI). We sought to describe 12-month outcomes following PCI in patients who would typically have undergone CABG. METHODS: Between March 1 and July 31, 2020, patients who received revascularization with PCI when CABG would have been the primary choice of revascularization were enrolled in the prospective, multicenter UK-ReVasc Registry. We evaluated the following major adverse cardiovascular events at 12 months: all-cause mortality, myocardial infarction, repeat revascularization, stroke, major bleeding, and stent thrombosis. RESULTS: A total of 215 patients were enrolled across 45 PCI centers in the United Kingdom. Twelve-month follow up data were obtained for 97% of the cases. There were 9 deaths (4.3%), 5 myocardial infarctions (2.4%), 12 repeat revascularizations (5.7%), 1 stroke (0.5%), 3 major bleeds (1.4%), and no cases of stent thrombosis. No difference in the primary endpoint was observed between patients who received complete vs incomplete revascularization (residual SYNTAX score £ 8 vs > 8) (P = .22). CONCLUSIONS: In patients with patterns of coronary disease in whom CABG would have been the primary therapeutic choice outside of the pandemic, PCI was associated with acceptable outcomes at 12 months of follow-up. Contemporary randomized trials that compare PCI to CABG in such patient cohorts may be warranted.

The effect of bariatric surgery on echocardiographic indices: a review of the literature.

Obesity is the new epidemic and is associated with an increased risk of diastolic and systolic heart failure. Effective treatment options with drastic results such as bariatric surgery have raised interest in the possible reversal of some of the cardiovascular sequelae. Many studies have assessed individually the effect of weight loss on specific echocardiographic indices, mostly employing nonhomogeneous groups. The purpose of this narrative review is to summarise the effect of bariatric surgery on echocardiographic indices of biventricular function and to help in the understanding of the expected echocardiographic changes in bariatric patients after weight-loss surgery.

Progressive Dilation of Coronary Artery Ectasia Causing Recurrent Myocardial Infarction.

We present a case of recurrent myocardial infarction with coronary artery ectasia that had progressive dilation. Both implanting drug-eluting stent and antithrombotic therapy with warfarin plus P2Y12 inhibitor were feasible. The careful follow-up including morphologic evaluation may be needed for this specific lesion. (Level of Difficulty: Intermediate.).

Coronary Slow Flow Is Not Diagnostic of Microvascular Dysfunction in Patients With Angina and Unobstructed Coronary Arteries.

Background Guidelines recommend that coronary slow flow phenomenon (CSFP), defined as corrected thrombolysis in myocardial infarction frame count (CTFC) >$$ > $$27, can diagnose coronary microvascular dysfunction (CMD) in patients with angina and nonobstructed coronary arteries. CSFP has also historically been regarded as a sign of coronary endothelial dysfunction (CED). We sought to validate the utility of CTFC, as a binary classifier of CSFP and as a continuous variable, to diagnose CMD and CED. Methods and Results Patients with angina and nonobstructed coronary arteries had simultaneous coronary pressure and flow velocity measured using a dual sensor-tipped guidewire during rest, adenosine-mediated hyperemia, and intracoronary acetylcholine infusion. CMD was defined as the inability to augment coronary blood flow in response to adenosine (coronary flow reserve <2.5) and CED in response to acetylcholine (acetylcholine flow reserve ≤1.5); 152 patients underwent assessment using adenosine, of whom 82 underwent further acetylcholine testing. Forty-six patients (30%) had CSFP, associated with lower flow velocity and higher microvascular resistance as compared with controls (16.5±$$ \pm $$6.9 versus 20.2±$$ \pm $$6.9 cm/s; P=0.001 and 6.26±$$ \pm $$1.83 versus 5.36±$$ \pm $$1.83 mm Hg/cm/s; P=0.009, respectively). However, as a diagnostic test, CSFP had poor sensitivity and specificity for both CMD (26.7% and 65.2%) and CED (21.1% and 56.0%). Furthermore, on receiver operating characteristics analyses, CTFC could not predict CMD or CED (area under the curve, 0.41 [95% CI, 0.32%-0.50%] and 0.36 [95% CI, 0.23%-0.49%], respectively). Conclusions In patients with angina and nonobstructed coronary arteries, CSFP and CTFC are not diagnostic of CMD or CED. Guidelines supporting the use of CTFC in the diagnosis of CMD should be revisited.