The role of coronary microvascular dysfunction in the pathogenesis of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a common condition with few effective therapies and hence represents a major healthcare burden. The clinical syndrome of HFpEF can be caused by varying pathophysiological processes, with coronary microvascular dysfunction (CMD) proposed as one of the aetiologies, although confirming causality has been challenging. CMD is characterised by the inability of the coronary vasculature to augment blood flow in response to a physiological stressor and has been established as the driver of angina in patients with non-obstructed coronaries (ANOCA), and this has subsequently led to efficacious endotype-directed therapies. CMD is also highly prevalent among sufferers of HFpEF and may represent a novel treatment target for this particular endotype of this condition. This review aims to discuss the role of the microcirculation in the healthy heart how it's dysfunction may precipitate HFpEF and explore the current diagnostic tools available. We also discuss the gaps in evidence and where we believe future research should be focussed.

Percutaneous Left Ventricular Unloading During High-Risk Coronary Intervention: Rationale and Design of the CHIP-BCIS3 Randomized Controlled Trial.

INTRODUCTION: Percutaneous coronary intervention for complex coronary disease is associated with a high risk of cardiogenic shock. This can cause harm and limit the quality of revascularization achieved, especially when left ventricular function is impaired at the outset. Elective percutaneous left ventricular unloading is increasingly used to mitigate adverse events in patients undergoing high-risk percutaneous coronary intervention, but this strategy has fiscal and clinical costs and is not supported by robust evidence. METHODS: CHIP-BCIS3 (Controlled Trial of High-Risk Coronary Intervention With Percutaneous Left Ventricular Unloading) is a prospective, multicenter, open-label randomized controlled trial that aims to determine whether a strategy of elective percutaneous left ventricular unloading is superior to standard care (no planned mechanical circulatory support) in patients undergoing nonemergent high-risk percutaneous coronary intervention. Patients are eligible for recruitment if they have severe left ventricular systolic dysfunction, extensive coronary artery disease, and are due to undergo complex percutaneous coronary intervention (to the left main stem with calcium modification or to a chronic total occlusion with a retrograde approach). Cardiogenic shock and acute ST-segment-elevation myocardial infarction are exclusions. The primary outcome is a hierarchical composite of all-cause death, stroke, spontaneous myocardial infarction, cardiovascular hospitalization, and periprocedural myocardial infarction, analyzed using the win ratio. Secondary outcomes include completeness of revascularization, major bleeding, vascular complications, health economic analyses, and health-related quality of life. A sample size of 250 patients will have in excess of 80% power to detect a hazard ratio of 0.62 at a minimum of 12 months, assuming 150 patients experience an event across all follow-up. CONCLUSIONS: To date, 169 patients have been recruited from 21 National Health Service hospitals in the United Kingdom, with recruitment expected to complete in 2024. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05003817.

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.

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.

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.

Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution.

Understanding the genetic and nongenetic determinants of tumor protein 53 (TP53)-mutation-driven clonal evolution and subsequent transformation is a crucial step toward the design of rational therapeutic strategies. Here we carry out allelic resolution single-cell multi-omic analysis of hematopoietic stem/progenitor cells (HSPCs) from patients with a myeloproliferative neoplasm who transform to TP53-mutant secondary acute myeloid leukemia (sAML). All patients showed dominant TP53 'multihit' HSPC clones at transformation, with a leukemia stem cell transcriptional signature strongly predictive of adverse outcomes in independent cohorts, across both TP53-mutant and wild-type (WT) AML. Through analysis of serial samples, antecedent TP53-heterozygous clones and in vivo perturbations, we demonstrate a hitherto unrecognized effect of chronic inflammation, which suppressed TP53 WT HSPCs while enhancing the fitness advantage of TP53-mutant cells and promoted genetic evolution. Our findings will facilitate the development of risk-stratification, early detection and treatment strategies for TP53-mutant leukemia, and are of broad relevance to other cancer types.

Coronary microvascular dysfunction and heart failure with preserved ejection fraction: what are the mechanistic links?

PURPOSE OF REVIEW: Heart failure with preserved ejection fraction (HFpEF) accounts for half of all heart failure presentations and is associated with a dismal prognosis. HFpEF is an umbrella term that constitutes several distinct pathophysiological entities. Coronary microvascular dysfunction (CMD), defined as the inability of the coronary vasculature to augment blood flow adequately in the absence of epicardial coronary artery disease, is highly prevalent amongst the HFpEF population and likely represents one distinct HFpEF endotype, the CMD-HFpEF endotype. This review appraises recent studies that have demonstrated an association between CMD and HFpEF with an aim to understand the pathophysiological links between the two. This is of significant clinical relevance as better understanding of the pathophysiology underlying CMD-HFpEF may result in more targeted and efficacious therapeutic options in this patient cohort. RECENT FINDINGS: There is a high prevalence of CMD, diagnosed invasively or noninvasively, in patients with HFpEF. Patients with HFpEF who have an impaired myocardial perfusion reserve (MPR) have a worse outcome than those with a normal MPR. Both MPR and coronary flow reserve (CFR) are associated with measures of left ventricular diastolic function and left ventricular filling pressures during exercise. Impaired lusitropy and subendocardial ischaemia link CMD and HFpEF mechanistically. SUMMARY: CMD-HFpEF is a prevalent endotype of HFpEF and one that is associated with adverse cardiovascular prognosis. Whether CMD leads to HFpEF, through subendocardial ischaemia, or whether it is secondary to the impaired lusitropy that is characteristic of HFpEF is not known. Further mechanistic work is needed to answer this pertinent question.

Development of artificial intelligence tools for invasive Doppler-based coronary microvascular assessment.

Aims: Coronary flow reserve (CFR) assessment has proven clinical utility, but Doppler-based methods are sensitive to noise and operator bias, limiting their clinical applicability. The objective of the study is to expand the adoption of invasive Doppler CFR, through the development of artificial intelligence (AI) algorithms to automatically quantify coronary Doppler quality and track flow velocity. Methods and results: A neural network was trained on images extracted from coronary Doppler flow recordings to score signal quality and derive values for coronary flow velocity and CFR. The outputs were independently validated against expert consensus. Artificial intelligence successfully quantified Doppler signal quality, with high agreement with expert consensus (Spearman's rho: 0.94), and within individual experts. Artificial intelligence automatically tracked flow velocity with superior numerical agreement against experts, when compared with the current console algorithm [AI flow vs. expert flow bias -1.68 cm/s, 95% confidence interval (CI) -2.13 to -1.23 cm/s, P < 0.001 with limits of agreement (LOA) -4.03 to 0.68 cm/s; console flow vs. expert flow bias -2.63 cm/s, 95% CI -3.74 to -1.52, P < 0.001, 95% LOA -8.45 to -3.19 cm/s]. Artificial intelligence yielded more precise CFR values [median absolute difference (MAD) against expert CFR: 4.0% for AI and 7.4% for console]. Artificial intelligence tracked lower-quality Doppler signals with lower variability (MAD against expert CFR 8.3% for AI and 16.7% for console). Conclusion: An AI-based system, trained by experts and independently validated, could assign a quality score to Doppler traces and derive coronary flow velocity and CFR. By making Doppler CFR more automated, precise, and operator-independent, AI could expand the clinical applicability of coronary microvascular assessment.

Minimal access awake craniotomy for drainage of cerebral abscess in a patient with severe complex cardiac defects in resource-limited country: A case report.

INTRODUCTION AND IMPORTANCE: Brain abscess is an uncommon but potentially fatal infection of the brain parenchyma that can affect 5 % to 18.7 % of people with uncorrected complex congenital heart defects. In management of patients with complex cardiac defects, the main concern is that they are prone to develop perioperative complications. Hence such cases are a real challenge for surgeons and anesthesiologists. In this study we have reported a well-managed awake craniotomy (Awake-Asleep-Awake) for drainage of cerebral abscess in a patient with complex cardiac defect. CASE PRESENTATION: We present a case of a 13-year-old male patient with untreated cyanotic CHD-TOF with complete AV canal defect, who complained of right-side paralysis since 2 weeks; and has been suffering from headache, fever and vomiting for 25 days. Brain CT scan showed a large abscess in the left fronto-temporal lobes. Minimal access awake craniotomy with regional scalp nerve block and sedation was done and about 100-120 cc thick pus was drained. The patient's paralysis improved significantly and neurological deficit ceased on 3rd postoperative day. CLINICAL DISCUSSION: Pediatric population itself is a challenge for anesthesiologists and this manifolds when associated with complex cardiac defects and neurosurgery cases. CONCLUSION: Brain abscess is expected to be more common in patients following uncorrected complex congenital heart disease in developing countries. Physicians must hold a high index of suspicion for early diagnosis and well-management of these patients with multidisciplinary approach. Minimal access awake craniotomy with or without sedation for patients with large brain abscess is a safe surgical approach.

Primary cervical hydatid cyst: A rare case report.

INTRODUCTION AND IMPORTANCE: Hydatid cyst is a zoonotic parasitic disease caused by Echinococcus granulosis. Occurrence in the head and neck is quite uncommon even in endemic areas. The diagnosis of an isolated cystic neck mass is still a challenge due to the presence of similar congenital cystic lesions and benign tumors in the neck. Imaging is useful, but sometimes they cannot identify a definitive diagnosis. The treatment of choice is exclusively surgical excision, combined with chemotherapy. Histopathology confirms the definitive diagnosis. CASE PRESENTATION: We present a case of an 8-year-old boy with no history of surgery or trauma, who complained of an isolated left posterior neck mass since one year. All radiological items lead to suspect a cystic lymphangioma. Excisional biopsy under general anesthesia was done. The cystic mass was totally resected and the diagnosis was further confirmed by histopathology. CLINICAL DISCUSSION: Cervical hydatid cyst is mostly a misdiagnosed condition, majority of hydatid cyst cases are asymptomatic and vary on the basis of their locations. The differential diagnosis includes cystic lymphangioma, branchial cleft cyst, bronchogenic, thoracic duct, esophageal duplication cysts, pseudocysts and benign tumors. CONCLUSION: Isolated cervical hydatid cyst is rarely reported yet, it must be considered in any cases of cystic cervical mass, particularly in endemic areas. Imaging modalities are sensitive in diagnosing cystic lesions, yet sometimes they cannot identify the exact etiology of the lesion. Furthermore, Prevention of hydatid disease is more favorable than surgical excision.

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.

Assessment and Management of Ischaemic Heart Disease in Non-Cardiac Surgery.

In the setting of non-cardiac surgery, cardiac complications contribute to over a third of perioperative deaths. With over 230 million major surgeries performed annually, and an increasing prevalence of cardiovascular risk factors and ischaemic heart disease, the incidence of perioperative myocardial infarction is also rising. The recent European Society of Cardiology guidelines on cardiovascular risk in noncardiac surgery elevated practices aiming to identify those at most risk, including biomarker monitoring and stress testing. However the current evidence base on if, and how, the risk of cardiac events can be modified is lacking. This review focuses on patient, surgical and cardiac risk assessment, as well as exploring the data on perioperative revascularization and other risk-reduction strategies.

Coronary Wave Intensity Analysis as an Invasive and Vessel-Specific Index of Myocardial Viability.

BACKGROUND: Coronary angiography and viability testing are the cornerstones of diagnosing and managing ischemic cardiomyopathy. At present, no single test serves both needs. Coronary wave intensity analysis interrogates both contractility and microvascular physiology of the subtended myocardium and therefore has the potential to fulfil the goal of completely assessing coronary physiology and myocardial viability in a single procedure. We hypothesized that coronary wave intensity analysis measured during coronary angiography would predict viability with a similar accuracy to late-gadolinium-enhanced cardiac magnetic resonance imaging. METHODS: Patients with a left ventricular ejection fraction ≤40% and extensive coronary disease were enrolled. Coronary wave intensity analysis was assessed during cardiac catheterization at rest, during adenosine-induced hyperemia, and during low-dose dobutamine stress using a dual pressure-Doppler sensing coronary guidewire. Scar burden was assessed with cardiac magnetic resonance imaging. Regional left ventricular function was assessed at baseline and 6-month follow-up after optimization of medical-therapy±revascularization, using transthoracic echocardiography. The primary outcome was myocardial viability, determined by the retrospective observation of functional recovery. RESULTS: Forty participants underwent baseline physiology, cardiac magnetic resonance imaging, and echocardiography, and 30 had echocardiography at 6 months; 21/42 territories were viable on follow-up echocardiography. Resting backward compression wave energy was significantly greater in viable than in nonviable territories (-5240±3772 versus -1873±1605 W m-2 s-1, P<0.001), and had comparable accuracy to cardiac magnetic resonance imaging for predicting viability (area under the curve 0.812 versus 0.757, P=0.649); a threshold of -2500 W m-2 s-1 had 86% sensitivity and 76% specificity. CONCLUSIONS: Backward compression wave energy has accuracy similar to that of late-gadolinium-enhanced cardiac magnetic resonance imaging in the prediction of viability. Coronary wave intensity analysis has the potential to streamline the management of ischemic cardiomyopathy, in a manner analogous to the effect of fractional flow reserve on the management of stable angina.

Aortic Valve Calcium Score Is Associated With Acute Stroke in Transcatheter Aortic Valve Replacement Patients.

Background: Transcatheter aortic valve replacement (TAVR) is the treatment of choice for patients with severe aortic stenosis who are at a moderate or higher surgical risk. Stroke is a recognised and serious complication of TAVR, and it is important to identify patients at higher stroke risk. This study aims to discover if aortic valve calcium score calculated from pre-TAVR computed tomography is associated with acute stroke in TAVR patients. Methods: We conducted a retrospective, observational cohort study of 433 consecutive patients undergoing TAVR between January 2017 and December 2019 at the Hammersmith Hospital. Results: This cohort had a median age of 83 years (interquartile range, 78-87), and 52.7% were male. Fifty-two patients (12.0%) had a history of previous stroke or transient ischemic attack. Median aortic valve calcium score was 2145 (interquartile range, 1427-3247) Agatston units. Twenty-two patients had a stroke up to the time of discharge (5.1%). In a logistic regression model, aortic valve calcium score was significantly associated with acute stroke (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.01-1.53; P = .02). Acute stroke was also significantly associated with peripheral arterial disease (OR, 4.32; 95% CI, 1.65-10.65; P = .0018) and a longer procedure time (OR, 1.01; 95% CI, 1.00-1.02; P = .0006). Conclusions: Aortic valve calcium score from pre-TAVR computed tomography is an independent risk factor for acute stroke in the TAVR population. This is an additional clinical value of the pre-TAVR aortic valve calcium score and should be considered when discussing periprocedural stroke risk.

Coronary Jeopardy Score Predicts Ischemic Etiology in Patients With Left Ventricular Systolic Dysfunction.

While cardiovascular magnetic resonance imaging (CMR) is the gold standard diagnostic test for heart failure etiology, it is not universally available. Our aim was to investigate whether quantifying the extent of coronary disease on angiography can predict the presence of an ischemic etiology. We included 176 patients who underwent CMR and coronary angiography for new heart failure with reduced ejection fraction. Based on CMR, 65% had an ischemic etiology and 35% were non-ischemic. A BCIS jeopardy score threshold ≥6 had 76% sensitivity and 97% specificity. In HFrEF, the extent of coronary disease on angiography can be used to rule in or out an ischemic etiology.

Comparison of Doppler Flow Velocity and Thermodilution Derived Indexes of Coronary Physiology.

OBJECTIVES: The aim of this study was to compare Doppler flow velocity and thermodilution-derived indexes and to determine the optimal thermodilution-based diagnostic thresholds for coronary flow reserve (CFR). BACKGROUND: The majority of clinical data and diagnostic thresholds for flow-based indexes are derived from Doppler measurements, and correspondence with thermodilution-derived indices remain unclear. METHODS: An international multicenter registry was conducted among patients who had coronary flow measurements using both Doppler and thermodilution techniques in the same vessel and during the same procedure. RESULTS: Physiological data from 250 vessels (in 149 patients) were included in the study. A modest correlation was found between thermodilution-derived CFR (CFRthermo) and Doppler-derived CFR (CFRDoppler) (r2 = 0.36; P < 0.0001). CFRthermo overestimated CFRDoppler (mean 2.59 ± 1.46 vs 2.05 ± 0.89; P < 0.0001; mean bias 0.59 ± 1.24 by Bland-Altman analysis), the relationship being described by the equation CFRthermo = 1.04 × CFRDoppler + 0.50. The commonly used dichotomous CFRthermo threshold of 2.0 had poor sensitivity at predicting a CFRDoppler value <2.5. The optimal CFRthermo threshold was 2.5 (sensitivity 75.54%, specificity 81.25%). There was only a weak correlation between hyperemic microvascular resistance and index of microvascular resistance (r2 = 0.19; P < 0.0001), due largely to variation in the measurement of flow by each modality. Forty-four percent of patients were discordantly classified as having abnormal microvascular resistance by hyperemic microvascular resistance (≥2.5 mm Hg · cm-1 · s) and index of microvascular resistance (≥25). CONCLUSIONS: CFR calculated by thermodilution overestimates Doppler-derived CFR, while both parameters show modest correlation. The commonly used CFRthermo threshold of 2.0 has poor sensitivity for identifying vessels with diminished CFR, but using the same binary diagnostic threshold as for Doppler (<2.5) yields reasonable diagnostic accuracy. There was only a weak correlation between microvascular resistance indexes assessed by the 2 modalities.

Invasive coronary physiology in patients with angina and non-obstructive coronary artery disease: a consensus document from the coronary microvascular dysfunction workstream of the British Heart Foundation/National Institute for Health Research Partnership.

Nearly half of all patients with angina have non-obstructive coronary artery disease (ANOCA); this is an umbrella term comprising heterogeneous vascular disorders, each with disparate pathophysiology and prognosis. Approximately two-thirds of patients with ANOCA have coronary microvascular disease (CMD). CMD can be secondary to architectural changes within the microcirculation or secondary to vasomotor dysfunction. An inability of the coronary vasculature to augment blood flow in response to heightened myocardial demand is defined as an impaired coronary flow reserve (CFR), which can be measured non-invasively, using imaging, or invasively during cardiac catheterisation. Impaired CFR is associated with myocardial ischaemia and adverse cardiovascular outcomes.The CMD workstream is part of the cardiovascular partnership between the British Heart Foundation and The National Institute for Health Research in the UK and comprises specialist cardiac centres with expertise in coronary physiology assessment. This document outlines the two main modalities (thermodilution and Doppler techniques) for estimation of coronary flow, vasomotor testing using acetylcholine, and outlines a standard operating procedure that could be considered for adoption by national networks. Accurate and timely disease characterisation of patients with ANOCA will enable clinicians to tailor therapy according to their patients' coronary physiology. This has been shown to improve patients' quality of life and may lead to improved cardiovascular outcomes in the long term.

Transcatheter Aortic Valve Replacement in Nonagenarians: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonagenarians represent only a small proportion of patients included in large transcatheter aortic valve replacement (TAVR) trials, but will become a relevant future population in need of treatment due to demographic change. Thus, this study sought to evaluate outcomes of TAVR for the treatment of severe aortic stenosis (AS) in nonagenarian patients. METHODS: We screened Medline/Pubmed for studies that stated specific outcomes for nonagenarians undergoing TAVR. A weighted meta-analysis was conducted, calculating pooled estimate rates using a binary random-effects model for dichotomous variables, and comparing non-dichotomous outcomes with a continuous random-effects model. RESULTS: Data from 23 studies including 16,094 nonagenarians were merged; 53.4% were women. Despite reasonable rates of comorbidities, Society of Thoracic Surgeons mortality risk score was 10.2 ± 5.4. Pooled estimate rate of procedural success was 94.1% (95% confidence interval [CI], 91.7-96.6), with major vascular complications occurring in 6.3% (95% CI, 2.7-9.8) and at least moderate postprocedural paravalvular leak in 7.5% (95% CI, 4.4-10.6). The rate of periprocedural stroke or transient ischemic attack was 2.6% (95% CI, 2.0-3.2). At 30 days, the pooled estimate of mortality was 6.1% (95% CI, 4.7-7.4) and a permanent pacemaker was implanted in 12.6% (95% CI, 7.6-17.6). After 1 year, the mortality rate was 20.5% (95% CI, 15.9-25.1). CONCLUSION: TAVR in nonagenarians is an effective and safe procedure, with encouraging outcomes given the general life expectancy of these patients. Currently, only selected nonagenarians are undergoing TAVR, but their number will grow as life expectancy continues to increase in the developed world. Specific research to identify ideal candidates and techniques in this cohort is needed.