Renin angiotensin system inhibitors and outcome in patients with takotsubo syndrome: A propensity score analysis of the GEIST registry.

BACKGROUND: Few data are available on long-term drug therapy and its potential prognostic impact after Takotsubo syndrome (TTS). Aim of the study is to evaluate clinical characteristics and long-term outcome of TTS patients on Renin Angiotensin system inhibitors (RASi). METHODS: TTS patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Median follow-up was 31 (Interquartile range 12-56) months. Comparison of RASi treated vs. untreated patients was performed within the overall population and after 1:1 propensity score matching for age, sex, comorbidities, type of trigger and in-hospital complications. REGISTRATION: clinicaltrials.gov, NCT04361994, https://clinicaltrials.gov/study/NCT04361994 RESULTS: Of the 2453 TTS patients discharged alive, 1683 (68%) received RASi therapy. Patients with RASi were older (age 71 ± 11 vs 69 ± 13 years, P = .01), with higher prevalence of hypertension (74% vs 53%, P < .01) and diabetes (19% v s15%, P = .01), higher admission left ventricular ejection fraction (LVEF) (41 ± 11% vs 39 ± 12%, P < .01) and lower rates of in-hospital complications (18.9% vs 29.6%, P < .01). At multivariable analysis, RASi therapy at discharge was independently associated with lower mortality (HR 0.63, 95% CI 0.45-0.87, P < .01). Survival analysis showed that at long term, patients treated with RASi had lower mortality rates in the overall cohort (log-rank P = .001). However, this benefit was not found among patients treated with RASi in the matched cohort (log-rank P = .168). Potential survival benefit of RASi were present, both in the overall and matched cohort, in 2 subgroups: patients with admission LVEF ≤ 40% (HR 0.54 95% CI 0.38-0.78, P = .001; HR 0.59, 95% CI 0.37-0.95, P = .030) and diabetes (HR 0.41, 95% CI 0.23-0.73, P = .002; HR 0.41, 95% CI 0.21-0.82, P = .011). CONCLUSIONS: Long-term therapy with RASi after a TTS episode was not associated with lower mortality rates at propensity score analysis. However, potential survival benefit can be found among patients with admission LVEF ≤ 40% or diabetes.

Takotsubo Syndrome: The Secret Crosstalk between Heart and Brain.

An acute, transient episode of left ventricular dysfunction characterizes Takotsubo syndrome. It represents about 2% of all cases of acute coronary syndrome (ACS), and occurs predominantly in postmenopausal women, generally following a significant physical or emotional stressor. It can be diagnosed based on clinical symptoms and the absence of coronary artery disease on angiography. Ventriculography remains the gold standard for the diagnosis. Despite its transitory characteristic Takotsubo syndrome should not be considered a benign condition since complications occur in almost half of the patients, and the mortality rate reaches 4-5%. Lately, it has been revealed that Takotsubo syndrome can also lead to permanent myocardial damage due to the massive release of catecholamines that leads to myocardial dysfunction. Different mechanisms have been advanced to explain this fascinating syndrome, such as plaque rupture and thrombosis, coronary spasm, microcirculatory dysfunction, catecholamine toxicity, and activation of myocardial survival pathways. Here are still several issues with Takotsubo syndrome that need to be investigated: the complex relationship between the heart and the brain, the risk of permanent myocardial damage, and the impairment of cardiomyocyte. Our review aims to elucidate the pathophysiology and the mechanisms underlying this complex disease to manage the diagnostic and therapeutic algorithms to create a functional synergy between physicians and patients.

A thymic hyperplasia-related reversible complete atrioventricular block: When compression is more important than compressor.

A 19-year-old patient presented for syncope with third-degree AV block (TDAVB) at ECG. A chest-CT showed a thymic mass that could be responsible for TDAVB due to extrinsic vagal nerve compression. Thymectomy led to complete AV block resolution. An extrinsic vagal compression mechanism should be considered among causes of complete atrioventricular block.

Prevalence, management, and outcome of adverse rhythm disorders in takotsubo syndrome: insights from the international multicenter GEIST registry.

One important complication related to takotsubo syndrome (TTS) is adverse rhythm disorders. Our study was conducted to determine the incidence and management of adverse rhythm disorders in TTS and its long-term prognostic impact. We analyzed 906 TTS patients from 9 European centers. Patients were divided into the adverse rhythm disorders group (encompassing ventricular tachycardia, ventricular fibrillation, torsade de pointes, and asystole or complete atrioventricular block) and non-adverse rhythm disorders group. In our study cohort, we identified 67 (7.4%) patients with presence of adverse rhythm disorders. TTS patients were followed up over a period of 2.8 years. In the adverse rhythm disorders group, 18% of patients presented adverse rhythm disorders before hospital admission. Asystole and/or AV block were significantly more presented before admission (13 patients versus 8 patients; p < 0.01), whereas ventricular tachyarrhythmias were more presented in-hospital (4 patients versus 42 patients; p < 0.01). Adverse rhythm disorders patients suffered more frequently from cardiogenic shock (31% versus 7.6%, p < 0.01) and in-hospital death (10.9% versus 3.6%; p < 0.01). Furthermore, the long-term survival was significantly impaired in adverse rhythm disorders patients as compared with non-adverse rhythm disorders patients; (log-rank p < 0.01). Using multivariate Cox regression analysis, cardiogenic shock (HR 2.86, 95% CI 1.1-6.9; p = 0.02) was identified as independent predictors of adverse rhythm disorders. The short- and long-term mortality rate of TTS patients presenting with adverse rhythm disorders was significantly higher than in TTS patients presenting without it. Therefore, TTS patients with adverse rhythm disorders should be carefully monitored during hospital stay and at long-term follow-up.

339 Interplay between COVID-19, pollution, and weather features on changes in the incidence of acute coronary syndromes in early 2020.

Aims: Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area. Methods and results: Italy was hit early on by COVID-19, such that state of emergency was declared on January 31, 2020, and national lockdown implemented on March 9, 2020, mainly because the accrual of cases in Northern Italy. In order to appraise the independent contribution on changes in STEMI and NSTEMI daily rates of COVID-19, climate and pollution, we collected data on these clinical events from tertiary care cardiovascular centers in the Lazio region and Rome metropolitan area. Multilevel Poisson modeling was used to appraise unadjusted and adjusted effect estimates for the daily incidence of STEMI and NSTEMI. The sample included 1448 STEMI and 2040 NSTEMI, with a total of 2882 PCI spanning 6 months. Significant reductions in STEMI and NSTEMI were evident already in early February 2020 (all P < 0.05), concomitantly with COVID-19 spread and institution of national countermeasures. Changes in STEMI and NSTEMI were inversely associated with daily COVID-19 tests, cases, and/or death (P < 0.05). In addition, STEMI and NSTEMI incidences were associated with daily NO2, PM10, and O3 concentrations, as well as temperature (P < 0.05). Multi-stage and multiply adjusted models highlighted that reductions in STEMI were significantly associated with COVID-19 data (P < 0.001), whereas changes in NSTEMI were significantly associated with both NO2 and COVID-19 data (both P < 0.001). Conclusion: Reductions in STEMI and NSTEMI in the COVID-19 pandemic may depend on different concomitant epidemiologic and pathophysiologic mechanisms. In particular, recent changes in STEMI may depend on COVID-19 scare, leading to excess all-cause mortality, or effective reduced incidence, whereas reductions in NSTEMI may also be due to beneficial reductions in NO2 emissions in the lockdown phase.

"Lambda-wave" ST-elevation is associated with severe prognosis in stress (takotsubo) cardiomyopathy.

BACKGROUND: Persistent ST-segment elevation in acute coronary syndrome is associated with both short and long-term complications. By contrast, there is limited information about ST-elevation and its evolution during takotsubo (stress) cardiomyopathy (TTC). AIM: To evaluate whether persistent downsloping ST-elevation in the early stages of TTC might correlate with short and long-term clinical events. METHODS: One-hundred fifty-eight consecutive subjects with TTC were prospectively enrolled and assessed by electrocardiogram. Patients were classified in two groups according to the presence of downsloping ST-elevation ≥5 mm lasting at least 24 hr ("lambda-wave" ST-elevation group vs. without downsloping ST-elevation) in at least one/two contiguous leads. RESULTS: Five (3.2%) patients, all female with a mean left ventricular ejection fraction 32 ± 5%, were included in the lambda-wave ST-elevation group. These patients were characterized by a higher prevalence of physical stressor (100% vs. 49%, p = 0.04) and higher admission and peak levels of troponin-I levels during hospitalization. Peak of ST-elevation in the lambda-wave ST-elevation group was reached 6 hr after admission and gradually decreased after 24 hr. In-hospital complications were observed in all the patients presenting lambda ST-elevation (100% vs. 23%, p = 0.03, OR: 29.1, p = 0.04); one patient presented endoventricular thrombosis and two died of cardiogenic shock. At long-term follow-up (mean 443 days), adverse events were observed in 80% of patients with lambda-wave ST-elevation (RR of adverse events at follow-up 32, p < 0.01). CONCLUSION: Persistent downsloping lambda-wave ST-elevation during the acute phase of stress cardiomyopathy may be associated with a higher risk of adverse events at short and long-term follow-up.

The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century.

Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician's experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio-renal interactions, and HF phenotypes.

Pacemaker dependency and conduction system recovery following transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI)-related conduction system disorders are dynamic and may resolve over time. The purpose of this study was to investigate predictive factors of PM dependency among patients receiving permanent PM implantation after TAVI. METHODS: We included 37 consecutive patients who underwent PPM implantation within six days after TAVI and who completed a 12-month follow-up. Patients were divided into two groups according to PPM dependency at follow-up: PPM-dependent group and non-PPM-dependent group. Device follow-ups were performed at one, six and 12 months. RESULTS: There were no significant differences in either baseline clinical characteristics or procedural data and results. Analysis of baseline ECGs showed a statistical difference in PR interval (200.1±17.2 ms in the PPM-dependent group vs. 175±23.3 ms in the non PPM-dependent group [P=0,003]) and in the presence of RBBB (four patients in the PPM-dependent group vs. no patients in the non PPM-dependent group [P=0.02]) as well as QRS duration (117.3±27.4 ms in the PPM-dependent group and 99±18.3 msec in the non PPM-dependent group [P=0.04]). CONCLUSIONS: The rate of PPM dependency was significantly reduced at 12-month follow-up: from 62,2% at the time of implantation to 35,1%. PR interval and RBBB were the most important predictive factors for PPM dependency. Persistent AVB and alternating BBB were prevalent in the PPM-dependent group. In the absence of persistent AVB or alternating BBB, we suggest that patients without long PR interval and RBBB at baseline ECG be carefully evaluated before permanent PM implantation, as conduction system recovery is possible.

Kidney Injury After Minimal Radiographic Contrast Administration in Patients With Acute Coronary Syndromes.

BACKGROUND: Acute kidney injury (AKI) is common in patients with acute coronary syndromes (ACS) treated by percutaneous coronary intervention. OBJECTIVES: Contrast media (CM) volume minimization has been advocated for prevention of AKI. The DyeVert CM diversion system (Osprey Medical, Inc) is designed to reduce CM volume during coronary procedures. METHODS: In this randomized, single-blind, investigator-driven clinical trial conducted in 4 Italian centers from February 4, 2020 to September 13, 2022, 550 participants with ACS were randomly assigned in a 1:1 ratio to the following: 1) the contrast volume reduction (CVR) group (n = 276), in which CM injection was handled by the CM diversion system; and 2) the control group (n = 274), in which a conventional manual or automatic injection syringe was used. The primary endpoint was the rate of AKI, defined as a serum creatinine (sCr) increase ≥0.3 mg/dL within 48 hours after CM exposure. RESULTS: There were 412 of 550 (74.5%) participants with ST-segment elevation myocardial infarction (211 of 276 [76.4%] in the CVR group and 201 of 274 [73.3%] in the control group). The CM volume was lower in the CVR group (95 ± 30 mL vs 160 ± 23 mL; P < 0.001). Seven participants (1 in the CVR group and 6 in the control group) did not have postprocedural sCr values. AKI occurred in 44 of 275 (16%) participants in the CVR group and in 65 of 268 (24.3%) participants in the control group (relative risk: 0.66; 95% CI: 0.47-0.93; P = 0.018). CONCLUSIONS: CM volume reduction obtained using the CM diversion system is effective for prevention of AKI in patients with ACS undergoing invasive procedures. (REnal Insufficiency Following Contrast MEDIA Administration TriaL IV [REMEDIALIV]: NCT04714736).

Holographic mixed reality for planning transcatheter aortic valve replacement.

BACKGROUND: Using three-dimensional (3D) modalities for optimal pre-procedure planning in transcatheter aortic valve replacement (TAVR) is critical for procedural success. However, current methods rely on visualizing images on a two-dimensional screen, using shading and colors to create the illusion of 3D, potentially impeding the accurate comprehension of the actual anatomy structures. In contrast, a new Mixed Reality (MxR) based software enables accurate 3D visualization, imaging manipulation, and quantification of measurements. AIMS: The study aims to evaluate the feasibility, reproducibility, and accuracy of dimensions of the aortic valve complex as measured with a new holographic MxR software (ARTICOR®, Artiness srl, Milano, Italy) compared to a widely used software for pre-operative sizing and planning (3mensio Medical Imaging BV, Bilthoven, The Netherlands). METHODS: This retrospective, observational, double-center study enrolled 100 patients with severe aortic stenosis who underwent cardiac computed tomography (CCT) before TAVR. The CCT datasets of volumetric aortic valve images were analyzed using 3Mensio and newly introduced MxR-based software. RESULTS: Ninety-eight percent of the CCT datasets were successfully converted into holographic models. A higher level of agreement between the two software systems was observed for linear metrics (short, long, and average diameter). In comparison, agreement was lower for area, perimeter, and annulus-to-coronary ostia distance measurements. Notably, the annulus area, annular perimeter, left ventricular outflow tract (LVOT) area, and LVOT perimeter were significantly and consistently smaller with the MxR-based software compared to the 3Mensio. Excellent interobserver reliability was demonstrated for most measurements, especially for direct linear measurements. CONCLUSIONS: Linear measurements of the aortic valve complex using MxR-based software are reproducible compared to the standard CCT dataset analyzed with 3Mensio. MxR-based software could represent an accurate tool for the pre-procedural planning of TAVR.

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry.

BACKGROUND AND AIMS: Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. METHODS: Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. RESULTS: Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74-1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04-1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20-2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83-3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68-3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62-3.10, p < 0.001) were associated with increased mortality. CONCLUSIONS: Statin therapy after a TTS event was not associated with better prognosis at follow-up.

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

Acute myocardial infarction in a patient with MELAS syndrome: a possible link?

The mitochondrial encephalomyopathy, lactic acidosis, and stroke (MELAS) syndrome is a mitochondrial disorder, commonly caused by m.3243A>G mutation in the MT-TL1 gene. It encodes for the mitochondrial leucine transfer RNA (tRNA Leu [UUR]), implicated in the translation of proteins involved in the assembly and function of mitochondrial complexes in the electron transport chain. The m.3243A>G mutation determines complex I (CI) deficiency, ultimately leading to NADH accumulation, higher rates of glycolysis in order to compensate for the reduced ATP production and increase in lactates, the end-product of glycolysis. Disruption of the oxidative phosphorylation function with an inability to produce sufficient energy results in multi-organ dysfunction, with high energy demanding cells, such as myocytes and neurons, being the most affected ones. Therefore, MELAS syndrome is characterized by a heterogeneous clinical spectrum. Here we report on a case of a 55-year-old man affected by MELA syndrome with no cardiovascular risk factors. He was admitted to our department because of a non ST-segment elevation myocardial infarction (NSTEMI). A coronary angioplasty of the posterior descending artery and of the left anterior descending artery was realized. Transthoracic echocardiography showed inferior and anterior left ventricular wall hypokinesis together with a moderate left ventricle hypertrophy. Cardiac involvement is reported in about a third of the patients and left ventricular hypertrophy (LVH) is the most common phenotype, with possible dilated cardiomyopathy in end-stage disease; brady- arrhythmias and tachy-arrhythmias are also frequently reported as well as Wolff- Parkinson-White (WPW) syndrome. Organ impairment and clinical manifestations depend on the heteroplasmy level of mutant DNA in cells that can differ among individuals, explaining why some patients present a more severe disease. A clear relationship between MELAS syndrome and atherosclerosis has never been established, however recently advocated. In vitro studies in MELAS patients have shown that higher mitochondrial ROS levels and increased expression of oxidative stress-related genes, as a consequence of complex I deficiency and disrupted electron transport, allow circulating LDL to be promptly oxidized into ox-LDL, contributing to endothelial dysfunction and atherosclerosis plaque formation. In light of the recent evidence suggesting a possible link between mitochondrial disorders and atherosclerosis, we speculate that MELAS syndrome may have played a role in the pathogenesis of coronary artery disease in our patient. Further investigations are needed to confirm a pathogenetic link.

Contrast Media Volume Control and Acute Kidney Injury in Acute Coronary Syndrome: Rationale and Design of the REMEDIAL IV Trial.

Background: Although the pathogenesis of acute kidney injury (AKI) in patients with acute coronary syndrome (ACS) undergoing invasive treatment is multifactorial, the role of iodinated contrast media (CM) has been well established. The DyeVert system (Osprey Medical) is designed to reduce the CM volume during invasive coronary procedures while maintaining fluoroscopic image quality. Objective: The aim of the Renal Insufficiency Following Contrast Media Administration Trial IV (REMEDIAL IV) is to test whether the use of the DyeVert system is effective in reducing contrast-associated acute kidney injury (CA-AKI) rate in patients with ACS undergoing urgent invasive procedures. Trial Design: Patients with ACS treated by urgent invasive approach will be enrolled. Participants will be randomly assigned into one of the following groups: (1) DyeVert group and (2) control group. In participants enrolled in the DyeVert group, CM injection will be handled by the DyeVert system. On the contrary, in the control group, CM injection will be performed by a conventional manual or automatic injection syringe. In all cases, iobitridol (a low-osmolar, nonionic CM) will be administered. Participants will receive intravenous 0.9% sodium chloride as soon as moved to the catheterization laboratory. The primary end points are CM volume administration and CA-AKI rate (ie, an increase in serum creatinine concentration of ≥0.3 mg/dL within 48 hours after CM exposure). A sample size of at least 522 randomized participants (261 in each group) is needed to demonstrate an 8.5% difference in the CA-AKI rate between the groups (that is, from 19% in the control group to 10.5% in the DyeVert group), with a 2-sided 95% confidence interval and 80% power (P < .05).

Intravenous volume expansion to prevent contrast-associated acute kidney injury.

OBJECTIVES: Several volume expansion protocols have been proposed to prevent contrast-associated acute kidney injury (CA-AKI). The aim of our study was to seek the ideal intravenous volume expansion to prevent CA-AKI in patients with chronic kidney disease (CKD) undergoing invasive cardiovascular procedures. METHODS: We analyzed 1927 CKD patients enrolled in 6 studies that took place from September 15, 2000 to June 6, 2019. Four volume expansion regiments were included: (1) conventional group (n=625); (2) bicarbonate group (n=255); (3) left ventricular end-diastolic pressure-guided group (n=355); and (4) urine flow rate-guided group (n=500). RESULTS: CA-AKI (serum creatinine increase ≥0.3 mg/dL at 48 hours) occurred in 224 (11%) patients. In patients with CA-AKI, volume expansion was lower (2090 ± 1382 mL vs 2551 ± 1716 mL; P less than .001) and acute pulmonary edema occurred more often (3.5% vs 0.29%; P less than .001). By ROC curve analysis, an absolute volume expansion greater than or equal to 1430 mL (AUC = 0.70) and a volume expansion to contrast media volume ratio greater than or equal to 17 (AUC = 0.57) were the best thresholds for freedom from CA-AKI. CONCLUSIONS: In our comprehensive pooled analysis, an absolute volume expansion greater than or equal to 1430 mL and a volume expansion to contrast media volume ratio greater than or equal to 17 are the best dichotomous thresholds for CA-AKI prevention. These cutoffs should be formally tested in a dedicated trial as a pragmatic means to prevent CA-AKI.

Trigger-Associated Clinical Implications and Outcomes in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

Background Takotsubo syndrome is usually triggered by a stressful event. The type of trigger seems to influence the outcome and should therefore be considered separately. Methods and Results Patients included in the GEIST (German-Italian-Spanish Takotsubo) registry were categorized according to physical trigger (PT), emotional trigger (ET), and no trigger (NT) of Takotsubo syndrome. Clinical characteristics as well as outcome predictors were analyzed. Overall, 2482 patients were included. ET was detected in 910 patients (36.7%), PT in 885 patients (34.4%), and NT was observed in 717 patients (28.9%). Compared with patients with PT or NT, patients with ET were younger, less frequently men, and had a lower prevalence of comorbidities. Adverse in-hospital events (NT: 18.8% versus PT: 27.1% versus ET: 12.1%, P<0.001) and long-term mortality rates (NT: 14.4% versus PT: 21.6% versus ET: 8.5%, P<0.001) were significantly lower in patients with ET. Increasing age (P<0.001), male sex (P=0.007), diabetes (P<0.001), malignancy (P=0.002), and a neurological disorder (P<0.001) were associated with a higher risk of long-term mortality, while chest pain (P=0.035) and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P=0.027) were confirmed as independent predictors for a lower risk of long-term mortality. Conclusions Patients with ET have better clinical conditions and a lower mortality rate. Increasing age, male sex, malignancy, a neurological disorder, chest pain, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and diabetes were confirmed as predictors of long-term mortality.

Impact of intra-aortic balloon counterpulsation on all-cause mortality among patients with Takotsubo syndrome complicated by cardiogenic shock: results from the German-Italian-Spanish (GEIST) registry.

Aims: Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction and can be complicated by cardiogenic shock (CS). However, few data are available on optimal care in TTS complicated by CS. Aim of this study was to evaluate short- and long-term impact of intra-aortic balloon pumping (IABP) on mortality in this setting. Methods and results: In a multi-centre, international registry on TTS, 2248 consecutive patients were enrolled from 38 centres from Germany, Italy, and Spain. Of the 2248 patients, 212 (9.4%) experienced CS. Patients with CS had a higher prevalence of diabetes (27% vs. 19%), male sex (25% vs. 10%), and right ventricular involvement (10% vs. 5%) (P < 0.01 in all cases). Forty-three patients with CS (20% of 212) received IABP within 8 h (interquartile range 4-18) after admission. No differences in terms of age, gender, cardiovascular risk factors, and admission left ventricular ejection fraction were found among patients with and without IABP. There were no significant differences in terms of 30-day mortality (16% vs. 17%, P = 0.98), length of hospitalization (18.9 vs. 16.7 days, P = 0.51), and need of invasive ventilation (35% vs. 41%, P = 0.60) among two groups: 30-day survival was not significantly different even after propensity score adjustment (log-rank P = 0.73). At 42-month follow-up, overall mortality in patients with CS and TTS was 35%, not significantly different between patients receiving IABP and not (37% vs. 35%, P = 0.72). Conclusions: In a large multi-centre observational registry, the use of IABP was not associated with lower mortality rates at short- and long-term follow-up in patients with TTS and CS.

Smoking influence in Takotsubo syndrome: insights from an international cohort.

Aims: To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS). Methods: Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted. Results: Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 ± 11 vs. 72 ± 11 years, p < 0.001), less frequently women (78% vs. 90%, p < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p < 0.01) and diabetes mellitus (16% vs. 20%, p = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p < 0.01) and/or psychiatric diseases (17% vs. 12%, p < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p = 0.97). Conclusions: Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality.

Reduction in emergency access for acute myocardial infarction during the COVID-19 pandemic: a survey from the greater area of Rome.

BACKGROUND: On March 9, 2020, the Italian government imposed a national lockdown to tackle the COronaVIrus Disease 19 (COVID-19) pandemic, including stay at home recommendations. The precise impact of COVID-19 scare and lockdown on emergency access for acute myocardial infarction (MI) is still subject to debate. METHODS: Data on all patients undergoing invasive coronary angiography at 9 hospitals in the greater area of Rome, Italy, between February 19, 2020 and March 29, 2020 were retrospectively collected. Incidence of ST-elevation MI (STEMI), and non-ST-elevation MI (NSTEMI), as well as corresponding percutaneous coronary intervention (PCI), was compared distinguishing two different 20-day time periods (before vs. on or after March 10, 2020). RESULTS: During the study period, 1068 patients underwent coronary angiography, 142 (13%) with STEMI and 169 (16%) with NSTEMI. The average daily number of STEMI decreased from 4.3 before the lockdown to 2.9 after the lockdown (P=0.021). Similarly, the average daily number of NSTEMI changed from 5.0 to 3.5 (P=0.028). The average daily number of primary PCI changed from 4.2 to 2.9 (P=0.030), while the average daily number of PCI for NSTEMI changed from 3.5 to 2.5 (P=0.087). For STEMI patients, the time from symptom onset to hospital arrival (onset-to-door time less than three hours) showed a significant increase after the lockdown (P=0.018), whereas door-to-balloon time did not change significantly from before to after the lockdown (P=0.609). CONCLUSIONS: The present study, originally reporting on the trends in STEMI and NSTEMI in the Rome area, highlights that significant decreases in the incidence of both acute coronary syndromes occurred between February 19, 2020 and March 29, 2020, together with increases in time from symptom onset to hospital arrival, luckily without changes in door-to-balloon time.