Rationale and Design of a Randomized Controlled Pilot Trial to Assess Stent Retriever Thrombectomy for Thrombus Burden Reduction in Patients with Acute Myocardial Infarction: The RETRIEVE-AMI Study.

BACKGROUND: ST-elevation myocardial infarction (STEMI) is typically caused by thrombotic occlusion of a coronary artery with subsequent hypoperfusion and myocardial necrosis. In approximately half of patients with STEMI, despite successful restoration of epicardial coronary patency, downstream myocardium perfusion remains impeded. Coronary microvascular injury is one of the key mechanisms behind suboptimal myocardial perfusion and it is primarily, yet not exclusively, related to distal embolization of atherothrombotic material following recanalization of the culprit artery. Routine manual thrombus-aspiration has failed to show clinical efficacy in this scenario. This could be related with limitations in technology adopted as well as patients' selection. To this end, we set out to explore the efficacy and safety of stent retriever-assisted thrombectomy based on clot-removal device routinely used in stroke intervention. STUDY DESIGN AND OBJECTIVES: The stent RETRIEVEr thrombectomy for thrombus burden reduction in patients with Acute Myocardial Infarction (RETRIEVE-AMI) study has been designed to establish whether stent retriever-based thrombectomy is safe and more efficacious in thrombus modification than the current standard of care: manual thrombus aspiration or stenting. The RETRIEVE-AMI trial will enrol 81 participants admitted for primary PCI for inferior STEMI. Participants will be 1:1:1 randomised to receive either standalone PCI, thrombus aspiration and PCI, or retriever-based thrombectomy and PCI. Change in thrombus burden will be assessed via optical coherence tomography imaging. A telephone follow-up at 6 months will be arranged. CONCLUSIONS: It is anticipated by the investigators that stent retriever thrombectomy will more effectively reduce the thrombotic burden compared to current standard of care whilst being clinically safe.

Erratum to "Case Series of Triathletes with Takotsubo Cardiomyopathy Presenting with Swimming-Induced Pulmonary Edema".

[This corrects the article DOI: 10.1155/2022/3602505.].

Case Series of Triathletes with Takotsubo Cardiomyopathy Presenting with Swimming-Induced Pulmonary Edema.

Objectives: To report three cases of triathletes who presented with swimming-induced pulmonary edema (SIPE) following water immersion. They were subsequently diagnosed with Takotsubo cardiomyopathy (TCM). Design: Retrospective case series. Method: All cases were recreational athletes competing in mass participation triathlons between June 2018 and 2019. They were initially managed by the event medical team and subsequently at the local tertiary level hospital. Written consent was gained from all the subjects. Results: The three triathletes were aged between 50 and 60 years, two were females, and all presented with acute dyspnoea on exiting the water. Two also presented with chest pain and haemoptysis. A diagnosis of SIPE was suspected by the medical event team on initial presentation of low oxygen saturations and clinical signs of pulmonary oedema. All were transferred to the local emergency department and had signs of pulmonary oedema on chest radiographs. Further investigations led to a diagnosis of TCM with findings of T wave inversion in anterolateral electrocardiogram leads and apical hypokinesia on transthoracic echocardiogram and unobstructed coronary arteries. Conclusions: This case series presents triathletes diagnosed with SIPE and TCM following the open water swim phase. It is unclear whether the myocardial dysfunction contributed to causation of SIPE or was the result of SIPE. Mass participation race organizers must be prepared that both SIPE and TCM can present in this population. Those presenting with an episode of SIPE require prompt evaluation of their cardiac and pulmonary physiology. Further research is required to ascertain the exact nature of the relationship between TCM and SIPE.

Long-Term Clinical Outcomes in Patients With an Acute ST-Segment-Elevation Myocardial Infarction Stratified by Angiography-Derived Index of Microcirculatory Resistance.

Aims: Despite the prognostic value of coronary microvascular dysfunction (CMD) in patients with ST-segment-elevation myocardial infarction (STEMI), its assessment with pressure-wire-based methods remains limited due to cost, technical and procedural complexities. The non-hyperaemic angiography-derived index of microcirculatory resistance (NH IMRangio) has been shown to reliably predict microvascular injury in patients with STEMI. We investigated the prognostic potential of NH IMRangio as a pressure-wire and adenosine-free tool. Methods and Results: NH IMRangio was retrospectively derived on the infarct-related artery at completion of primary percutaneous coronary intervention (pPCI) in 262 prospectively recruited STEMI patients. Invasive pressure-wire-based assessment of the index of microcirculatory resistance (IMR) was performed. The combination of all-cause mortality, resuscitated cardiac arrest and new heart failure was the primary endpoint. NH IMRangio showed good diagnostic performance in identifying CMD (IMR > 40U); AUC 0.78 (95%CI: 0.72-0.84, p < 0.0001) with an optimal cut-off at 43U. The primary endpoint occurred in 38 (16%) patients at a median follow-up of 4.2 (2.0-6.5) years. On survival analysis, NH IMRangio > 43U (log-rank test, p < 0.001) was equivalent to an IMR > 40U(log-rank test, p = 0.02) in predicting the primary endpoint (hazard ratio comparison p = 0.91). NH IMRangio > 43U was an independent predictor of the primary endpoint (adjusted HR 2.13, 95% CI: 1.01-4.48, p = 0.047). Conclusion: NH IMRangio is prognostically equivalent to invasively measured IMR and can be a feasible alternative to IMR for risk stratification in patients presenting with STEMI.

Angiography-derived index of microcirculatory resistance (IMRangio) as a novel pressure-wire-free tool to assess coronary microvascular dysfunction in acute coronary syndromes and stable coronary artery disease.

To investigate the diagnostic accuracy of (1) hyperaemic angiography-derived index of microcirculatory resistance (IMRangio) in defining coronary microvascular dysfunction (CMD) across patients with acute coronary syndromes (ST-elevation myocardial infarction [STEMI]; non-ST elevation acute coronary syndrome [NSTE-ACS]) and stable chronic coronary syndrome [CCS]) and (2) the accuracy of non-hyperaemic IMRangio (NH-IMRangio) to detect CMD in STEMI. 145 patients (STEMI = 66; NSTEMI = 43; CCS = 36) were enrolled. 246 pressure-wire IMR measurements were made in 189 coronary vessels. IMRangio and NH-IMRangio was derived using quantitative flow ratio. In patients with STEMI, cardiac magnetic resonance was performed to quantify microvascular obstruction (MVO). IMRangio was correlated with IMR (overall rho = 0.78, p < 0.0001; STEMI, rho = 0.85 p < 0.0001; NSTE-ACS and rho = 0.72, p < 0.0001; CCS, rho = 0.70, p < 0.0001) and demonstrated good diagnostic performance in predicting high IMR (STEMI AUCROC = 0.93 [0.88-0.98]; NSTE-ACS AUCROC = 0.77 [0.63-0.92]; CCS AUCROC = 0.88 [0.79-0.97]). Agreement between the two indices was evident on Bland Altman analysis. In STEMI, NH-IMRangio was also well correlated with IMR (rho = 0.64, p < 0.0001), with good diagnostic accuracy in predicting high invasive IMR (AUCROC = 0.82 [0.74-0.90]). Both IMRangio (AUCROC = 0.74 [0.59-0.89]) and NH-IMRangio (AUCROC = 0.76 [0.54-0.87]) were significantly associated with MVO in STEMI. In conclusions, IMRangio is a valid alternative to invasive IMR to detect CMD in patients with acute and stable coronary syndromes, whilst NH-IMRangio has a good diagnostic accuracy in STEMI where it could become a user-friendly diagnostic tool as it is adenosine-free.

Angiography-derived index of microcirculatory resistance as a novel, pressure-wire-free tool to assess coronary microcirculation in ST elevation myocardial infarction.

Immediate assessment of coronary microcirculation during treatment of ST elevation myocardial infarction (STEMI) may facilitate patient stratification for targeted treatment algorithms. Use of pressure-wire to measure the index of microcirculatory resistance (IMR) is possible but has inevitable practical restrictions. We aimed to develop and validate angiography-derived index of microcirculatory resistance (IMRangio) as a novel and pressure-wire-free index to facilitate assessment of the coronary microcirculation. 45 STEMI patients treated with primary percutaneous coronary intervention (pPCI) were enrolled. Immediately before stenting and at completion of pPCI, IMR was measured within the infarct related artery (IRA). At the same time points, 2 angiographic views were acquired during hyperaemia to measure quantitative flow ratio (QFR) from which IMRangio was derived. In a subset of 15 patients both IMR and IMRangio were also measured in the non-IRA. Patients underwent cardiovascular magnetic resonance imaging (CMR) at 48 h for assessment of microvascular obstruction (MVO). IMRangio and IMR were significantly correlated (ρ: 0.85, p < 0.001). Both IMR and IMRangio were higher in the IRA rather than in the non-IRA (p = 0.01 and p = 0.006, respectively) and were higher in patients with evidence of clinically significant MVO (> 1.55% of left ventricular mass) (p = 0.03 and p = 0.005, respectively). Post-pPCI IMRangio presented and area under the curve (AUC) of 0.96 (CI95% 0.92-1.00, p < 0.001) for prediction of post-pPCI IMR > 40U and of 0.81 (CI95% 0.65-0.97, p < 0.001) for MVO > 1.55%. IMRangio is a promising tool for the assessment of coronary microcirculation. Assessment of IMR without the use of a pressure-wire may enable more rapid, convenient and cost-effective assessment of coronary microvascular function.

Hyper-acute cardiovascular magnetic resonance T1 mapping predicts infarct characteristics in patients with ST elevation myocardial infarction.

BACKGROUND: Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). METHODS: STEMI patients underwent 3 T cardiovascular magnetic resonance (CMR), within 3 h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3 h was compared with changes at 24-h to predict final infarct size. RESULTS: Forty patients were included in this study. Patients with average T1 values of AAR ≥1400 ms within 3 h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P = 0.003) and at 6-months (27% ±9 vs. 12% ±9; P < 0.001), higher incidence and larger extent of MVO (85% vs. 40%, P = 0.016) & [4.0 (0.5-9.5)% vs. 0 (0-3.0)%, P = 0.025]. The average T1 value was an independent predictor of acute LGE (ß 0.61, 95%CI 0.13 to 1.09; P = 0.015), extent of MVO (ß 0.22, 95%CI 0.03 to 0.41, P = 0.028) and final infarct size (ß 0.63, 95%CI 0.21 to 1.05; P = 0.005). Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE > 9.5%) with 100% positive predictive value at the optimal cut-off of 1400 ms (area-under-the-curve, AUC 0.88, P = 0.006). CONCLUSION: Hyper-acute T1 values of the AAR (within 3 h post PPCI, but not 24 h) predict a larger extent of MVO and infarct size at both 24 h and 6 months follow-up. Delayed CMR scanning for 24 h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics.

Beyond patency: Functional assessment of adequacy using internal mammary artery grafting to the left anterior descending artery.

INTRODUCTION: Arterial graft physiology influences the long-term outcome of coronary artery bypass grafting (CABG). We studied factors that can affect the overall resistance to flow using internal mammary artery grafting to the left anterior descending artery. METHODS: This was a prospective, nonrandomized observational study of 100 consecutive patients who underwent elective on-pump isolated or combined valve surgery and CABG. Coronary stenoses were assessed using conventional and quantitative coronary angiography assessment. The flow and pulsatility index (PI) of the grafts were assessed by transit-time flowmetry during cardioplegic arrest and at the end of the operation. Fractional polynomials were used to explore linearity, followed by multivariable regression analysis. RESULTS: Univariate analysis demonstrated higher flows at the end of the operation in patients who had higher flows with the cross-clamp on (P < .001), in males (P = .004), in patients with a low PI at the end of the operation (P = .04), and in patients with a larger size of the recipient artery (P = .005). Multivariable regression analysis showed that the graft flow at the end of the operation was significantly associated with the mean flow with the cross-clamp on (P < .001), sex (P = .003), and PI at the end of the operation (P = .003). Concomitant valve surgery did not influence flows. Male patients had 18 mL/min higher flow. CONCLUSIONS: The graft flow at the end of the operation can be determined by the flow with the cross-clamp on, the PI with the cross-clamp off and coronary artery. We reported differences in the graft flows between sexes, and for first the time, we introduced the concepts of "adequate flow" and "resistance-to-forward-flow" for patent coronary grafts.

Safety of Rotational Atherectomy Using the Radial Access in Patients With Severe Aortic Stenosis.

Despite frequent percutaneous coronary intervention (PCI) in calcified vessels of older patients, rotational atherectomy (RA) has not been endorsed in patients with severe aortic stenosis (AS) due to safety concerns and lack of data. We explored periprocedural safety and mortality in severe AS patients undergoing RA. Prospective anonymized clinical, echocardiographic, procedural and outcome data of patients undergoing RA PCI between January 2012 and July 2018 were retrospectively extracted from the institutional coronary database. Patients with severe AS undergoing RA PCI were 1:1 propensity matched with patients undergoing RA PCI in the absence of AS. Outcomes of interest were RA related periprocedural complications, 30-day and 1-year mortality. A prespecified subgroup analysis examined the influence of transcatheter aortic valve replacement on mortality following RA PCI. A total of 544 patients underwent RA PCI; 478 without AS and 66 with AS. Propensity matching yielded 35 matched pairs with improved balance in covariates of interest and no significant differences in baseline characteristics postmatching. In the matched cohort (n = 70) slow flow/no-reflow, coronary dissection, perforation, and hemodynamic instability were rare and not significantly different. Survival analyses revealed significantly higher 30-day (Log-Rank p = 0.02) and 1-year mortality (Log rank p = 0.02, HR 5.24 [95% CI 1.13 to 24.28]) in the severe AS group; driven by a fivefold increase in the hazard of death among patients who did not undergo transcatheter aortic valve replacement HR 4.98 [95% CI 1.03 to 24.1]. In conclusion, our study of 70 patients undergoing radial RA PCI suggests that it can be safely performed in patients with severe AS. Long-term outcomes after RA in patients with severe AS are determined by the presence of the valve disease and other co-morbidities.

Incremental Value of Coronary Microcirculation Resistive Reserve Ratio in Predicting the Extent of Myocardial Infarction in Patients with STEMI. Insights from the Oxford Acute Myocardial Infarction (OxAMI) Study.

BACKGROUND: Resistive reserve ratio (RRR) is a novel index that expresses the ratio between basal and hyperemic microcirculatory resistance. We sought to compare the performance of RRR, coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in predicting the extent of infarct size (IS) after ST-elevation myocardial infarction. METHODS: Thermodilution parameters were measured after primary percutaneous coronary intervention (PPCI) in 45 patients. In 30 (67%) cases pre-stenting measurements were also performed to assess the effect of PPCI on myocardial reperfusion, defined by CFR. Cardiovascular magnetic resonance (CMR) was performed at 48-h to assess area-at-risk (AAR), microvascular obstruction (MVO) and IS. CMR was repeated at 6 months in 39/45 patients. RESULTS: RRR (AUCRRR = 0.85, CI: 0.71-0.99) performed better compared to CFR (AUCCFR = 0.67, CI: 0.48-0.86) and IMR (AUCIMR = 0.70, CI: 0.52-0.88) in predicting IS% at 6-months. Patients with impaired RRR showed larger acute-IS% (27.4 [14.5-42.5] vs 15.4 [8.3-26], p = 0.018), MVO% (3.44 [0-5.97] vs 0 [0-0.89], p = 0.026), AAR% (43 [35-52] vs 34 [25-46], p = 0.03) and 6-months-IS% (22.7 [10.2-35] vs 8.8 [6.9-12.3], p = 0.006), higher rate of adverse remodeling (22.2% vs 0%, p = 0.04) and lower myocardial salvage index (34% [22.8-59.2] vs 53.2% [37.7-71], p = 0.032) compared with other patients. Furthermore, RRR but not IMR or CFR resulted independently associated with 6-months-IS%. CFR (1.48 ±â€¯0.87 vs 1.47 ±â€¯0.61, p = 0.94) did not improve after PPCI in patients with impaired RRR, whereas it improved significantly in other patients (CFR: 1.37 ±â€¯0.43 vs 1.93 ±â€¯0.49, p = 0.018). CONCLUSIONS: Patients with post-PPCI impaired RRR were more likely to have suboptimal myocardial reperfusion and larger IS at follow-up. RRR may offer incremental prognostic value compared with other thermodilution-derived indices.

Index of Microcirculatory Resistance as a Tool to Characterize Microvascular Obstruction and to Predict Infarct Size Regression in Patients With STEMI Undergoing Primary PCI.

OBJECTIVES: This study aimed to compare the value of the index of microcirculatory resistance (IMR) and microvascular obstruction (MVO) measured by cardiac magnetic resonance (CMR) in patients treated for and recovering from ST-segment elevation myocardial infarction. BACKGROUND: IMR can identify patients with microvascular dysfunction acutely after primary percutaneous coronary intervention (pPCI), and a threshold of >40 has been shown to be associated with an adverse clinical outcome. Similarly, MVO is recognized as an adverse feature in patients with ST-segment elevation myocardial infarction. Even though both IMR and MVO reflect coronary microvascular status, the interaction between these 2 parameters is uncertain. METHODS: A total of 110 patients treated with pPCI were included, and IMR was measured immediately at completion of pPCI. Infarct size (IS) as a percentage of left ventricular mass was quantified at 48 h (38.4 ± 12.0 h) and 6 months (194.0 ± 20.0 days) using CMR. MVO was identified and quantified at 48 h by CMR. RESULTS: Overall, a discordance between IMR and MVO was observed in 36.7% of cases, with 31 patients having MVO and IMR ≤40. Compared with patients with MVO and IMR ≤40, patients with both MVO and IMR >40 had an 11.9-fold increased risk of final IS >25% at 6 months (p = 0.001). Patients with MVO and IMR ≤40 had a significantly smaller IS at 6 months (p = 0.001), with significant regression in IS over time (34.4% [interquartile range (IQR): 27.3% to 41.0%] vs. 22.3% [IQR: 16.0% to 30.0%]; p = 0.001). CONCLUSIONS: Discordant prognostic information was obtained from IMR and MVO in nearly one-third of cases; however, IMR can be helpful in grading the degree and severity of MVO.

Index of microcirculatory resistance-guided therapy with pressure-controlled intermittent coronary sinus occlusion improves coronary microvascular function and reduces infarct size in patients with ST-elevation myocardial infarction: the Oxford Acute Myocardial Infarction - Pressure-controlled Intermittent Coronary Sinus Occlusion study (OxAMI-PICSO study).

AIMS: The Oxford Acute Myocardial Infarction PICSO (OxAMI-PICSO) study aimed to assess the efficacy of index of microcirculatory resistance (IMR)-guided therapy with pressure-controlled intermittent coronary sinus occlusion (PICSO) in anterior ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Patients with anterior STEMI treated with primary percutaneous coronary intervention (pPCI) were enrolled. Pre-stenting IMR was measured and PICSO treatment delivered if pre-stenting IMR was >40. No PICSO treatment was considered in patients with a pre-stenting IMR ≤40. The control group was derived from a historical cohort of STEMI patients with pre-stenting IMR >40 enrolled in the observational OxAMI study. IMR was measured after completion of pPCI in all patients and within 48 hours in PICSO patients and controls. Cardiac magnetic resonance imaging was performed per protocol for infarct size (IS) assessment within 48 hours after pPCI and at six months. A total of 105 patients were enrolled (25 PICSO, 50 controls with pre-stenting IMR >40, 30 with pre-stenting IMR ≤40). Compared to controls, patients treated with PICSO had a lower IMR at 24-48 hours (24.8 [18.5-35.9] vs. 45.0 [32.0-51.3], p<0.001) and lower IS at six months (26.0% [20.2-30.0] vs. 33.0% [28.0-37.0], p=0.006). CONCLUSIONS: An IMR-guided treatment with PICSO in anterior STEMI is feasible and may be associated with reduced IS and improved microvascular function.

The ATI score (age-thrombus burden-index of microcirculatory resistance) determined during primary percutaneous coronary intervention predicts final infarct size in patients with ST-elevation myocardial infarction: a cardiac magnetic resonance validation study.

AIMS: The age-thrombus burden-index of microcirculatory resistance (ATI) score is a diagnostic tool able to predict suboptimal myocardial reperfusion before stenting, in patients with ST-elevation myocardial infarction (STEMI). We aimed to validate the ATI score against cardiac magnetic resonance imaging (cMRI). METHODS AND RESULTS: The ATI score was calculated prospectively in 80 STEMI patients. cMRI was performed within 48 hours in all patients and in 50 patients at six-month follow-up to assess the extent of infarct size (IS%) and microvascular obstruction (MVO%). The ATI score was calculated using age (>50=1 point), pre-stenting index of microcirculatory resistance (IMR) (>40 and <100=1 point; ≥100=2 points) and angiographic thrombus score (4=1 point; 5=3 points). ATI score was closely related to final IS% (ATI.

Inhaled Nanoparticles Accumulate at Sites of Vascular Disease.

The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2-200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials.

Fire Simulation and Cardiovascular Health in Firefighters.

BACKGROUND: Rates of myocardial infarction in firefighters are increased during fire suppression duties, and are likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assessed the effects of simulated fire suppression on measures of cardiovascular health in healthy firefighters. METHODS: In an open-label randomized crossover study, 19 healthy firefighters (age, 41±7 years; 16 males) performed a standardized training exercise in a fire simulation facility or light duties for 20 minutes. After each exposure, ex vivo thrombus formation, fibrinolysis, platelet activation, and forearm blood flow in response to intra-arterial infusions of endothelial-dependent and -independent vasodilators were measured. RESULTS: After fire simulation training, core temperature increased (1.0±0.1°C) and weight reduced (0.46±0.14 kg, P<0.001 for both). In comparison with control, exposure to fire simulation increased thrombus formation under low-shear (73±14%) and high-shear (66±14%) conditions (P<0.001 for both) and increased platelet-monocyte binding (7±10%, P=0.03). There was a dose-dependent increase in forearm blood flow with all vasodilators (P<0.001), which was attenuated by fire simulation in response to acetylcholine (P=0.01) and sodium nitroprusside (P=0.004). This was associated with a rise in fibrinolytic capacity, asymptomatic myocardial ischemia, and an increase in plasma cardiac troponin I concentrations (1.4 [0.8-2.5] versus 3.0 [1.7-6.4] ng/L, P=0.010). CONCLUSIONS: Exposure to extreme heat and physical exertion during fire suppression activates platelets, increases thrombus formation, impairs vascular function, and promotes myocardial ischemia and injury in healthy firefighters. Our findings provide pathogenic mechanisms to explain the association between fire suppression activity and acute myocardial infarction in firefighters. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01812317.

Effects of the small molecule SIRT1 activator, SRT2104 on arterial stiffness in otherwise healthy cigarette smokers and subjects with type 2 diabetes mellitus.

OBJECTIVE: Arterial stiffness increases with age, and is associated with adverse cardiovascular outcome including increased mortality. The effect of the oral small molecule SIRT1 activator, SRT2104, on arterial stiffness was examined in otherwise healthy cigarette smokers and participants with type 2 diabetes mellitus. METHODS: 24 otherwise healthy cigarette smokers and 15 people with stable type 2 diabetes were randomised in a double-blind placebo-controlled crossover trial and received 28 days of oral SRT2104 (2.0 g/day) or matched placebo. Blood pressure was measured using non-invasive oscillatory sphygmomanometry. Pulse wave analysis and velocity were measured using applanation tonometry at baseline and the end of each treatment period. Owing to the small sample size and similar trends for both groups, data for the two groups were pooled (post hoc analysis). RESULTS: Compared to placebo, treatment with SRT2104 was associated with a significant reduction in augmentation pressure (p=0.0273) and a trend towards improvement in the augmentation index and corrected augmentation index (p>0.05 for both). However, no changes were observed in pulse wave velocity and time to wave reflection (p>0.05). Systolic and diastolic blood pressures remained unchanged throughout the study. Treatment by cohort interaction was not significant for any of the pulse wave parameters, suggesting that the response to SRT2104 in otherwise healthy smokers and people with diabetes was consistent. CONCLUSIONS: SRT2104 may improve measures of arterial stiffness in otherwise healthy cigarette smokers and in participants with type 2 diabetes. Definitive conclusions are not possible given the small sample size and exploratory nature of this analysis. TRIAL REGISTRATION NUMBER: NCT01031108.