A novel therapy in microvascular obstruction in ST-elevation myocardial infarction: pressure-controlled intermittent coronary sinus occlusion therapy.

Percutaneous coronary intervention has transformed the management of ST-elevation myocardial infarction (STEMI) due to a reduction in early mortality and need for repeat revascularization. However, the conventional revascularization strategy, combined with state-of-the-art anti-thrombotic and antiplatelet therapies, can still be associated with poor clinical outcome in some patients, because of reperfusion injury and microvascular obstruction contributing to the infarct size. To address this important therapeutic need, a broad-range of device-based treatments have been introduced. This is an overview of the pressure-controlled intermittent coronary sinus occlusion (PiCSO) device (Miracor Medical SA) which has been proposed for STEMI patients. PiCSO therapy could lead to an improved perfusion, decrease microvascular dysfunction, and thus potentially reduce infarct size.

A technology evaluation of the Onyx Frontier drug-eluting stent.

INTRODUCTION: Onyx FrontierTM represents the latest iteration within the family of zotarolimus-eluting stents (ZES), designed for the treatment of coronary artery disease. Approval by the Food and Drug Administration was granted in May 2022, and Conformité Européenne marking followed in August 2022. AREAS COVERED: We hereby review the principal design features of Onyx Frontier, highlighting differences and similarities with other currently available drug-eluting stents. In addition, we focus on the refinements of this newest platform as compared with previous ZES versions, including the attributes yielding its exceptional crossing profile and deliverability. The clinical implications related to both its newest and inherited characteristics will be discussed. EXPERT OPINION: The nuances of the latest Onyx Frontier, together with the continuous refinement previously witnessed throughout the development of ZES, lead to a latest generation device ideal for a diverse spectrum of clinical and anatomical scenarios. In particular, its peculiarities will be of benefit in the settings often offered by a progressively aging population, such as high bleeding risk patients and complex coronary lesions.

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial.

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective: To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, Setting, and Participants: The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions: Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main Outcomes and Measures: The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Results: Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). Conclusions and Relevance: In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04401293.

Treatment-Dose LMWH versus Prophylactic/Intermediate Dose Heparins in High-Risk COVID-19 Inpatients: Rationale and Design of the HEP-COVID Trial.

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15-30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.

Targeting the safe zone: A quality improvement project to reduce vascular access complications.

OBJECTIVE: The aim of this study was to assess the effectiveness of a quality improvement (QI) program in reducing vascular complications during cardiac catheterization. BACKGROUND: Vascular access complications during cardiac catheterization are associated with higher morbidity and mortality. We implemented a QI program focused on using micropuncture techniques and targeting the "safe zone," an area below the inferior border of the inferior epigastric artery and above the inferior border of the femoral head, for femoral artery puncture. METHODS: Our catheterization laboratory implemented a protocol that required all operators to use micro puncture technique during diagnostic and/or percutaneous coronary interventions and to document arteriotomy in the "safe zone." We also encouraged use of vascular ultrasound, radial artery approach, and increased use of vascular closure devices (VCDS). We analyzed data on 3120 patients (2013, pre-QI cohort) and 3222 patients (2014, QI cohort). Data on vascular complications were prospectively collected and compared with the rate of complications that occurred during the same time one year prior when the QI project was not in effect. RESULTS: Baseline characteristics of two cohorts of patients were similar. Compliance with the protocol was excellent. Appropriate documentation of the wire exiting the needle was observed in 95% of cases. VCD use increased from 35% in 2013 to 60% in 2014 (P < 0.001) There were no significant differences in the overall number of complications after implementation of the QI project (1.03% complications before QI implementation and 0.96% after QI implementation. P = 0.79) but there was an absolute reduction in the number of hematomas (0.77 vs. 0.40% in 2013 vs. 2014, respectively, P = 0.06) and of pseudoaneurysms (0.35 vs. 0.19% P = 0.20). Correlates of major vascular complications included), age > 75 years (HR 3.1, P < 0.0001), and PCI (vs. diagnostic cath). CONCLUSIONS: Micropuncture technique in association with "safe zone targeting "did not significantly reduce vascular complications in patients undergoing cardiac catheterization, but a trend toward decrease of hematomas and pseudoaneurysms was noted. Factors such as age and type of procedure (PCI vs. diagnostic) play a significant role in the occurrence of vascular complications. © 2017 Wiley Periodicals, Inc.

Deep Vein Thrombosis of the Left Leg: A Case of May-Thurner Syndrome.

A 56-year-old woman presented with gradually worsening shortness of breath associated with dull left leg pain over 5 days. She denied any recent travel, recent surgeries or immobilization. CT pulmonary angiography and CT venography revealed multiple bilateral pulmonary emboli and extensive left pelvic and left lower extremity deep vein thromboses. Contrast-enhanced CT showed that the right common iliac artery crossed the left common iliac vein and compressed it externally, indicative of May-Thurner syndrome. Catheter-directed thrombolysis of the left lower extremity was performed and heparin infusion was started. The patient also underwent left iliac vein balloon angioplasty with stenting and infra-renal inferior vena cava filter placement via the jugular approach to prevent further embolization. LEARNING POINTS: May-Thurner syndrome (MTS) should be suspected in patients in their second to fourth decade of life presenting with unprovoked deep venous thrombosis of the left leg.An iliac venogram is the diagnostic test of choice for MTS.MTS is treated only when it is symptomatic. The goal of treatment is to remove the clot to prevent post-thrombotic syndrome and to repair the anatomical defect.A stent was successfully deployed in the iliac vein of our patient and restoration of blood flow resulted in a dramatic improvement in the patient's symptoms.

Host immunity shapes the impact of climate changes on the dynamics of parasite infections.

Global climate change is predicted to alter the distribution and dynamics of soil-transmitted helminth infections, and yet host immunity can also influence the impact of warming on host-parasite interactions and mitigate the long-term effects. We used time-series data from two helminth species of a natural herbivore and investigated the contribution of climate change and immunity on the long-term and seasonal dynamics of infection. We provide evidence that climate warming increases the availability of infective stages of both helminth species and the proportional increase in the intensity of infection for the helminth not regulated by immunity. In contrast, there is no significant long-term positive trend in the intensity for the immune-controlled helminth, as immunity reduces the net outcome of climate on parasite dynamics. Even so, hosts experienced higher infections of this helminth at an earlier age during critical months in the warmer years. Immunity can alleviate the expected long-term effect of climate on parasite infections but can also shift the seasonal peak of infection toward the younger individuals.

From door-to-balloon time to contact-to-device time: predictors of achieving target times in patients with ST-elevation myocardial infarction.

BACKGROUND: The 2013 American College of Cardiology Foundation/American Heart Association ST-segment elevation myocardial infarction (STEMI) guidelines have shifted focus from door-to-balloon (D2B) time to the time from first medical contact to device activation (contact-to-device time [C2D] ). HYPOTHESIS: This study investigates the impact of prehospital wireless electrocardiogram transmission (PHT) on reperfusion times to assess the impact of the new guidelines. METHODS: From January 2009 to December 2012, data were collected on STEMI patients who received percutaneous coronary interventions; 245 patients were included for analysis. The primary outcome was median C2D time in the PHT group and the secondary outcome was D2B time. RESULTS: Prehospital wireless electrocardiogram transmission was associated with reduced C2D times vs no PHT: 80 minutes (interquartile range [IQR], 64-94) vs 96 minutes (IQR, 79-118), respectively, P < 0.0001. The median D2B time was lower in the PHT group vs the no-PHT group: 45 minutes (IQR, 34-56) vs 63 minutes (IQR, 49-81), respectively, P < 0.0001. Multivariate analysis showed PHT to be the strongest predictor of a C2D time of <90 minutes (odds ratio: 3.73, 95% confidence interval: 1.65-8.39, P = 0.002). Female sex was negatively predictive of achieving a C2D time <90 minutes (odds ratio: 0.23, 95% confidence interval: 0.07-0.73, P = 0.01). CONCLUSIONS: In STEMI patients, PHT was associated with significantly reduced C2D and D2B times and was an independent predictor of achieving a target C2D time. As centers adapt to the new guidelines emphasizing C2D time, targeting a shorter D2B time (<50 minutes) is ideal to achieve a C2D time of <90 minutes.

Adrenergic activation, fuel substrate availability, and insulin resistance in patients with congestive heart failure.

OBJECTIVES: This study sought to investigate plasma levels of glucose and free fatty acids (FFA) and their relationship with adrenergic activation and insulin resistance (IR) in patients with advanced congestive heart failure (CHF). BACKGROUND: Adrenergic activation and IR are hallmarks of advanced heart failure. The resulting changes in fuel substrate availability and their implications for exercise capacity have not been elucidated. METHODS: Subjects with CHF underwent maximal exercise testing. Plasma glucose, FFA, insulin, and norepinephrine (NE) levels were measured at rest and at peak exercise. Beta-receptor sensitivity to NE was assessed using the Chronotropic Responsiveness Index (CRI). Homeostasis Model Assessment Index >2.5 defined IR. Left ventricular ejection fraction was estimated by 2-dimensional echocardiography. RESULTS: Ninety-six subjects were enrolled. CHF subjects without IR (CHF/No-IR), but not those with IR (CHF/IR), significantly increased glucose and insulin in response to exercise. Only CHF/No-IR subjects increased FFA in response to exercise (0.14 ± 0.27 mmol/l; p = 0.027). NE increased significantly less with exercise, and CRI was lower in CHF/IR subjects compared with CHF/No-IR subjects (1.3 ± 1.4 vs. 2.5 ± 2.1; 6.4 ± 2.6 vs. 8.5 ± 3.4; p = 0.069). CRI correlated with the exercise-induced increase in FFA (r = 0.41; p < 0.005). These results stayed the same after excluding diabetic patients from the CHF/IR group. CONCLUSIONS: Circulating FFA levels increased during exercise in CHF subjects without IR, but not in those with IR or DM. Increased FFA availability during exercise may represent a catecholamine-dependent compensatory fuel shift in CHF.

Effect of ß-blocker cessation on chronotropic incompetence and exercise tolerance in patients with advanced heart failure.

BACKGROUND: Chronotropic incompetence is defined as the inability to reach 80% of heart rate (HR) reserve or 80% of the maximally predicted HR during exercise. The presence of chronotropic incompetence is associated with reduced peak oxygen consumption, and rate-responsive pacing therapy is under investigation to improve exercise capacity in heart failure (HF). However, uncertainty exists about whether chronotropic incompetence and reduced exercise tolerance in HF are attributable to ß-blockade. METHODS AND RESULTS: Subjects with HF and receiving long-term ß-blocker therapy underwent cardiopulmonary exercise tolerance testing under 2 conditions in random sequence: (1) after a 27-hour washout period (Off-BB) and (2) 3 hours after ß-blocker ingestion (On-BB). Norepinephrine levels were drawn at rest and at peak exercise. ß1-response to norepinephrine was assessed using the chronotropic responsiveness index: ΔHR/Δlog norepinephrine. Nineteen patients with systolic HF (left ventricular ejection fraction, 22.8±7.7%) were enrolled. Mean age was 49.4±12.3 years. Average carvedilol equivalent dose was 29.1±17.0 mg daily. Peak HR off/on ß-blockers was 62.7±18.7% and 51.4±18.2% HR reserve (P<0.01) and 79.1±11.0% and 70.3±12.3% maximally predicted HR (P<0.01). For the Off-BB and On-BB conditions, the respiratory exchange ratios were 1.05±0.06 and 1.05±0.10 (P=0.77), respectively, confirming maximal and near identical effort in both conditions. The peak oxygen consumption was 16.6±3.34 and 15.9±3.31 mL/kg/min (P=0.03), and the chronotropic responsiveness index was 19.3±7.2 and 16.2±7.1 (P=0.18). CONCLUSIONS: Acute ß-blocker cessation does not normalize the chronotropic response to exercise in patients with advanced HF and chronotropic incompetence.

Rate responsive pacing using cardiac resynchronization therapy in patients with chronotropic incompetence and chronic heart failure.

AIMS: Chronotropic incompetence (CI) is a common finding in patients with advanced chronic heart failure (CHF) and is associated with a worse functional capacity. Whether rate responsive pacing with cardiac resynchronization therapy (CRT) would acutely improve exercise performance in patients with advanced CHF and severe CI (<70% age-predicted maximum heart rate) is unknown. METHODS AND RESULTS: Patients (n = 13) with CHF, a CRT device, and severe CI were randomized in a double-blind crossover pilot study to either DDD (control) or DDDR (rate responsive) pacing. Six minutes walk test (6MWT) distance, oxygen consumption at anaerobic threshold (VO(2) @ AT), and maximal oxygen consumption (VO(2) max) were measured. One week later, testing was repeated in the alternate pacing mode. Rate responsive pacing commenced with standard settings in only 9 of 13 (69%) patients. In these 9 subjects, 6MWT distance improved acutely from 358.5 ± 40.7 to 376.8 ± 24.5 m with DDDR pacing (P< 0.05). VO(2) max did not improve with DDDR pacing (14.0 ± 3.2 mL/kg/min) compared with DDD pacing (13.9 ± 3.0 mL/kg/min; P= 0.69). VO(2) @ AT tended towards improvement with DDDR pacing (10.8 ± 2.9 mL/kg/min) compared with DDD pacing (9.6 ± 1.8 mL/kg/min; P= 0.29). There was a linear relationship between the increase in heart rate at minute 3 during rate responsive pacing and improvement in VO(2) @ AT (r = 0.83, P< 0.05). CONCLUSION: When rate responsive pacing using a CRT device is achieved in patients with advanced CHF and severe CI, parameters of aerobic exercise performance improve acutely. Routine exercise testing to ensure successful restoration of heart rate response may be beneficial to optimize CRT settings in this patient population.

Effect of acute ß-blocker withholding on ventilatory efficiency in patients with advanced chronic heart failure.

BACKGROUND: This is the first study to examine the effect of acute (24-hour) beta-blocker withholding on ventilatory efficiency in patients with advanced chronic heart failure (CHF) during maximal incremental treadmill cardiopulmonary exercise test. METHODS AND RESULTS: Seventeen CHF patients were studied either 3 hours after administration of beta-blocker (BB(ON)) or 27 hours after the last beta-blocker ingestion (BB(OFF)). The ventilatory efficiency was measured via the slope of the linear relationship between ventilation (V'(E)) and carbon dioxide production (V'CO2) (ie, V'(E)/V'CO2 slope). Measurements were also made at rest, anaerobic threshold (AT), maximal end-tidal pressure for carbon dioxide (P(ET)CO2max), respiratory compensation point (RC), and peak exercise. Compared with BB(ON), the V'(E)/V'CO2 slope was significantly increased during BB(OFF) (30.8 +/- 7.4 vs. 29.1 +/- 5.4, P = .04). At peak exercise, oxygen uptake (V'O2, 16.0 +/- 2.7 vs. 15.6 +/- 2.8 mL x kg x min) and V'CO2 (1458 +/- 459 vs. 1414 +/- 429 mL/min) were not different between the 2 conditions, whereas V'(E) was higher during BB(OFF) (49.5 +/- 10.7 vs. 46.1 +/- 9.6 L/min, P = .04). No differences were noted at AT and RC in V'O2, V'CO2, V'(E), V'(E)/V'O2, and V'(E)/V'CO2 ratios during the 2 conditions. At P(ET)CO2max, used to noninvasively estimate the CO2 set point, V'(E) was higher (33.9 +/- 7.6 vs. 31.7 +/- 7.3 L/min, P = .002) and P(ET)CO2 was lower (37.4 +/- 4.8 vs. 38.5 +/- 4.0 mm Hg, P = .03), whereas V'CO2 was unchanged (1079 +/- 340 vs. 1050 +/- 322 mL/min) during BB(OFF). CONCLUSION: Acute beta-blocker withholding resulted in decreased ventilatory efficiency mostly from an increase of V'CO2-independent regulation of V'(E) and less likely from a change in ventilation/perfusion mismatching.

Utilization of defibrillators and resynchronization therapy at the time of evaluation at a heart failure and cardiac transplantation center.

BACKGROUND: Internal cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) reduce mortality, but are underutilized in routine clinical practice. The use of these devices in patients at the time of an initial evaluation at an advanced heart failure and cardiac transplantation center is unknown. METHODS: We retrospectively analyzed consecutive patients who were enrolled in a database examining parameters of cardiopulmonary exercise testing in chronic heart failure (CHF) patients at the time of an initial outpatient evaluation at a tertiary care center. Rates of ICD and CRT use in eligible patients were determined. RESULTS: Two hundred two patients had an average age of 54 +/- 13 years and an average peak oxygen consumption (pVO(2)) of 12.5 +/- 4.5 mL/kg/min. Of 97 patients eligible for an ICD only, 57% had an ICD at the time of evaluation. Sixty-four percent of ICD-eligible male patients had an ICD compared to 36% of ICD-eligible female patients (P = 0.015). Of 105 patients meeting criteria for CRT, 54% had a CRT device. There was no difference between CRT use in eligible male and female patients. CONCLUSIONS: ICDs and CRT are underutilized in patients with severe CHF at the time of evaluation at a tertiary care center despite young age, objective functional limitation, and active consideration for advanced CHF therapies. Female patients have lower rates of ICD use than male patients.

Resting heart rate does not reflect the degree of beta-blockade in subjects with heart failure on chronic beta-blocker therapy.

We investigated the relationship between resting heart rate (HR) and two measures of beta-1 receptor sensitivity/blockade: (1) the percentage of maximal predicted heart rate reached during exercise (%MPHR), and (2) the HR increase per unit of circulating norepinephrine (NE) or the chronotropic responsiveness index (CRI) in 28 patients with systolic CHF on chronic beta-blocker therapy. Our results show that resting HR is not associated with HR response during exercise nor with beta-1 receptor sensitivity to circulating NE.

Annular-to-leaflet mismatch and the need for reductive annuloplasty in patients undergoing mitral repair for chronic mitral regurgitation due to mitral valve prolapse.

Annular dilation is a common feature of chronic degenerative mitral regurgitation caused by leaflet prolapse. Accordingly, patients undergoing surgical repair usually undergo concomitant reductive annuloplasty to restore a normal annular-to-leaflet relation. With the evolution of transcatheter valve repair technologies, patient selection criteria for those who do not require annuloplasty are needed. A series of patients undergoing mitral repair was analyzed, and the role of annular-to-leaflet mismatch in identifying patients requiring reductive annuloplasty was explored. Preoperative data for 82 patients undergoing mitral repair with annuloplasty for degenerative mitral regurgitation were prospectively collected, including annular intercommissural (IC) and septolateral (SL) dimensions and heights of anterior (ALH) and posterior leaflets. An SL/ALH ratio >1.4 was used to define annular-to-leaflet mismatch. After mitral repair, the ratio between preoperative IC distance and the size of the implanted annular prosthesis (Seguin ring [SR], IC/SR <1.2) was used to identify patients for whom annuloplasty was nonreductive. All patients underwent successful mitral repair. Mean preoperative IC was 46 +/- 6 mm, SL was 42 +/- 5 mm, and ALH was 31 +/- 5 mm. Mean SR was 34 +/- 3 mm, with a mean IC/SR ratio of 1.34 +/- 0.14. Sixteen patients (19%) had an IC/SR ratio <1.2. IC/SR ratio <1.2 was predicted by a SL/ALH ratio < or =1.4 (p = 0.009). In conclusion, annular dilation is negligible in <20% of surgical candidates. In this subgroup, an isolated leaflet repair may be indicated. SL/ALH ratio is a good indicator of annular-to-leaflet mismatch and could be used as an adjunct to other methods of annular function assessment to select patients for ringless mitral repair.