Comparison of MANTA versus Perclose Prostyle large-bore vascular closure devices during transcatheter aortic valve implantation.

BACKGROUND: New vascular closure devices (VCD) are being introduced for achieving hemostasis after transcatheter aortic valve implantation (TAVI). However, no safety or efficacy data have been published compared to other contemporary VCD. AIM: To compare the safety and efficacy of suture-based Perclose Prostyle as compared to plug-based MANTA device. METHODS: A total of 408 consecutive TAVI patients from two high volume TAVI centers were included in the present study. Patients were grouped according to VCD: Prostyle versus MANTA. Propensity score matching (PSM) and multivariable analysis were utilized to compare clinical endpoints between the two groups. The primary endpoint was any vascular complication (VC) according to VARC-3 criteria. RESULTS: After PSM, a total of 264 patients were analyzed, of them 132 in each group. Overall baseline characteristics of the two groups were comparable. Primary end-point was similar between MANTA as compared to Prostyle (16.7% vs. 15.3% respectively, p = 0.888). The main driver for VC among MANTA group were minor vascular complications (15.2%). Conversely, minor and major VC contributed equally to the primary endpoint among Prostyle group (7.6%) (p = 0.013). No outcome predictors were identified in multivariate analysis. CONCLUSIONS: VCD for transfemoral TAVI using the new-generation Prostyle device or the MANTA device achieved comparable VARC-3 VC rates.

Conservative, surgical, and percutaneous treatment for mitral regurgitation shortly after acute myocardial infarction.

AIMS: Severe mitral regurgitation (MR) following acute myocardial infarction (MI) is associated with high mortality rates and has inconclusive recommendations in clinical guidelines. We aimed to report the international experience of patients with secondary MR following acute MI and compare the outcomes of those treated conservatively, surgically, and percutaneously. METHODS AND RESULTS: Retrospective international registry of consecutive patients with at least moderate-to-severe MR following MI treated in 21 centres in North America, Europe, and the Middle East. The registry included patients treated conservatively and those having surgical mitral valve repair or replacement (SMVR) or percutaneous mitral valve repair (PMVR) using edge-to-edge repair. The primary endpoint was in-hospital mortality. A total of 471 patients were included (43% female, age 73 ± 11 years): 205 underwent interventions, of whom 106 were SMVR and 99 PMVR. Patients who underwent mitral valve intervention were in a worse clinical state (Killip class ≥3 in 60% vs. 43%, P < 0.01), but yet had lower in-hospital and 1-year mortality compared with those treated conservatively [11% vs. 27%, P < 0.01 and 16% vs. 35%, P < 0.01; adjusted hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.18-0.46, P < 0.01]. Surgical mitral valve repair or replacement was performed earlier than PMVR [median of 12 days from MI date (interquartile range 5-19) vs. 19 days (10-40), P < 0.01]. The immediate procedural success did not differ between SMVR and PMVR (92% vs. 93%, P = 0.53). However, in-hospital and 1-year mortality rates were significantly higher in SMVR than in PMVR (16% vs. 6%, P = 0.03 and 31% vs. 17%, P = 0.04; adjusted HR 3.75, 95% CI 1.55-9.07, P < 0.01). CONCLUSIONS: Early intervention may mitigate the poor prognosis associated with conservative therapy in patients with post-MI MR. Percutaneous mitral valve repair can serve as an alternative for surgery in reducing MR for high-risk patients.

Beneficial effect of awake prone position in hypoxaemic patients with COVID-19: case reports and literature review.

We hereby present two case reports of moderate coronavirus disease patients, suffering from profound hypoxaemia, further deteriorating later on. A schedule pre-planned awake prone position manoeuvres were executed during their hospital stay. Following this, the patients' saturation improved, later to be weaned from oxygen support. Paucity of evidence and data regarding this topic led us to review the concept of awake prone position.

The impact of diabetes mellitus on the clinical phenotype of hypertrophic cardiomyopathy.

AIMS: Diabetes mellitus (DM) aggravates the clinical features of ischaemic and hypertensive heart diseases and worsens the prognosis of heart failure patients. Hypertrophic cardiomyopathy (HCM) and diabetes coexist fairly frequently in elderly patients but the impact of DM on the clinical phenotype of HCM is yet unknown. We sought to describe if predominant features of heart failure in DM patients exist independently in HCM. METHODS AND RESULTS: We reviewed clinical characteristics of 937 patients, age ≥40, diagnosed with HCM, from two tertiary medical centres in Spain and Israel. A propensity score matched cohort of 294 patients was also analysed. Our cohort comprised 102 HCM patients with diabetes (8.7%). Patients with DM were older at diagnosis {median 56 [interquartile range (IQR) 47-67] vs. 53 (IQR 43-63), P = 0.02} and had a higher prevalence of comorbidities. Hypertrophic cardiomyopathy patients with DM had a higher prevalence of diastolic dysfunction, pulmonary hypertension, significant mitral regurgitation, and pacemaker implantation. Hypertrophic cardiomyopathy patients with DM had a higher New York Heart Association (NYHA) class (P < 0.001) and lower exercise capacity [7.0 METS (IQR 5.0-10.0) vs. 9.0 METS (IQR 6.6-11.0), P = 0.002]. These findings were independent of age, gender, country of origin, hypertension, and coronary artery disease. Patients with diabetes had a significantly higher 15-year mortality (22% vs. 15%, P = 0.03), with no differences in sudden cardiac death, appropriate implanted cardioverter-defibrillator therapy, or heart transplantation. CONCLUSION: Hypertrophic cardiomyopathy patients with diabetes are older and have a higher cardiovascular risk profile. They have a lower functional capacity and more heart failure symptoms due to diastolic dysfunction.

Clinical Characterization of 162 COVID-19 patients in Israel: Preliminary Report from a Large Tertiary Center.

BACKGROUND: In February 2020, the World Health Organisation designated the name COVID-19 for a clinical condition caused by a virus identified as a cause for a cluster of pneumonia cases in Wuhan, China. The virus subsequently spread worldwide, causing havoc to medical systems and paralyzing global economies. The first COVID-19 patient in Israel was diagnosed on 27 February 2020. OBJECTIVES: To present our findings and experiences as the first and largest center for COVID-19 patients in Israel. METHODS: The current analysis included all COVID-19 patients treated in Sheba Medical Center from February 2020 to April 2020. Clinical, laboratory, and epidemiological data gathered during their hospitalization are presented. RESULTS: Our 162 patient cohort included mostly adult (mean age of 52 ± 20 years) males (65%). Patients classified as severe COVID-19 were significantly older and had higher prevalence of arterial hypertension and diabetes. They also had significantly higher white blood cell counts, absolute neutrophil counts, and lactate dehydrogenase. Low folic acid blood levels were more common amongst severe patients (18.2 vs. 12.9 vs. 9.8, P = 0.014). The rate of immune compromised patients (12%) in our cohort was also higher than in the general population. The rate of deterioration from moderate to severe disease was high: 9% necessitated non-invasive oxygenation and 15% were intubated and mechanically ventilated. The mortality rate was 3.1. CONCLUSIONS: COVID-19 patients present a challenge for healthcare professionals and the whole medical system. We hope our findings will assist other providers and institutions in their care for these patients.

Personalized diabetes management recommendations at hospital discharge based on a computerized, pre-hospitalization clinical profile analysis: A prospective, electronic health records-based study.

BACKGROUND: While glycemic control of hospitalized diabetic patients is straightforward, personalization of management at discharge is challenging. Treatment guidelines base recommendations on the clinical profile of patients. We checked the feasibility of implementing discharge recommendations, based on the clinical profile in the patients' electronic health records (EHR). METHODS: A decision-making algorithm was devised according to current guidelines. It was incorporated into the EHR. A prospective follow-up of eligible diabetes patients was done. RESULTS: During 15 months, 835 patients (HbA1c was 6.9% [6.2%-7.8%]) met our inclusion criteria. The rate of HbA1c acquisition increased from 55% during Q1 to 85%, 86%, 88%, and 87% thereafter. Also, the rate of incorporating personalized management recommendations to discharge letters increased: from 14.9% during Q1 to 42.9%, 43.0%, 47.2%, and 53.4% thereafter. Fifty-eight (17.3%) of patients who got personalized recommendations upon discharge were found to have HbA1c values that were over 1% deviating from suggested target HbA1c. They got the most stringent recommendations. Twenty-nine (50%) of them had available follow-up HbA1c values showing a significant drop in HbA1c: from 9.1% (8.4%-10.2%) to 8.5% (7.4%-9.5%), P = .03. CONCLUSIONS: Personalized, EHR algorithm-based, management recommendations for diabetes upon discharge from hospitalization are feasible and beneficial.

Structured, Protocol-Based Pulse-Oximetry Measurement Improves the Evaluation of Hypoxemic Patients at Hospital Admission.

BACKGROUND: Accurate pulse oximetry reading at hospital admission is of utmost importance, mainly for patients presenting with hypoxemia. Nevertheless, there is no accepted or evidence-based protocol for such structured measuring. OBJECTIVES: To devise and assess a structured protocol intended to increase the accuracy of pulse oximetry measurement at hospital admission. METHODS: The authors performed a prospective comparison of protocol-based pulse-oximetry measurement with non-protocol based readings in consecutive patients at hospital admission. They also calculated the relative percentage of improvement for each patient (before and after protocol implementation) as a fraction of the change in peripheral capillary oxygen saturation (SpO2) from 100%. RESULTS: A total of 460 patients were recruited during a 6 month period. Implementation of a structured measurement protocol significantly changed saturation values. The SpO2 values of 24.7% of all study participants increased after protocol implementation (ranging from 1% to 21% increase in SpO2 values). Among hypoxemic patients (initial SpO2 < 90%), protocol implementation had a greater impact on final SpO2 measurements, increasing their median SpO2 readings by 4% (3-8% interquartile range; P < 0.05). Among this study population, 50% of the cohort improved by 17% of their overall potential and 25% improved by 50% of their overall improvement potential. As for patients presenting with hypoxemia, the median improvement was 31% of their overall SpO2 potential. CONCLUSIONS: Structured, protocol based pulse-oximetry may improve measurement accuracy and reliability. The authors suggest that implementation of such protocols may improve the management of hypoxemic patients.

Low ALT blood levels are associated with lower baseline fitness amongst participants of a cardiac rehabilitation program.

BACKGROUND/OBJECTIVE: Objective assessment tools for patients' frailty are lacking. Such tools would have been highly valuable for assessment of candidates for cardiac rehabilitation programs. Low ALT (Alanine aminotransferase) values were recently shown to be a promising parameter for objective, quantitative frailly assessment. METHODS: This was a retrospective study of patients participating in a cardiac rehabilitation program. RESULTS: Patients with lower ALT activity levels at the initiation of rehabilitation program had lower estimated METs values (6.86 vs. 7.73; p < 0.001), shorter stress test duration (06:41 vs. 07:44 min; p < 0.001), higher resting heart rate (72 ± 13 vs. 70 ± 13 BPM; p = 0.01) and lower heart rate reserve (49 ± 24 vs. 54 ± 24; p < 0.001). Multivariate linear modeling demonstrated that ALT values were Independent determinants of baseline exercise capacity (expressed in METs). CONCLUSION: Lower ALT values, measured prior to the initiation of cardiac rehabilitation programs may indicate frailty of patients and be indicative for poor rehabilitation outcomes. Further, prospective studies should assess the potential correlation between ALT values and rehabilitation efficiency. We aimed to assess the potential correlation between the baseline ALT values and the baseline exercise capacity, as expressed in METs (Metabolic equivalent of tasks). 3806 patients were included in our study.

The role of direct single monetary grants in residents' choice of field of residency.

BACKGROUND: In an attempt to address severe medical manpower shortages in several medical disciplines, the Israeli Ministry of Health offered grants to residents who chose one of these fields. METHODS: A total of 220 residents from various disciplines were surveyed on demographic, academic, and professional data, and asked to rank considerations in the choice of their field of residency. RESULTS: Residents in targeted fields attributed significantly more importance to the grant in their decision-making process (U = 3704.5, p < 0.001). This effect remained significant in a multivariate model (OR 1.67, 95%CI 1.32-2.10, p < 0.001). Higher age (OR 1.15, 95%CI 1.01-1.31, p = 0.031) and attribution of significance to the working conditions compared to other residency fields (OR 1.69, 95%CI 1.23-2.32, p = 0.001) were significantly associated with receptivity toward the grant in a multivariate analysis. DISCUSSION: Receptivity toward the offered grants correlated with real-life data shows a rise in physician in these fields, and the weak association between such receptivity and most variables tested may suggest that the grants were perceived as a property of the specific choice rather than a special bonus. CONCLUSIONS: Grants may be useful in diverting medical manpower. Further analysis and modeling are required to determine causal relationship and budgetary feasibility.

Pericarditis recurrence is associated with milder electrocardiographic, echocardiographic, and laboratory findings.

Recurrent pericarditis (RP) complicates approximately 30% of acute pericarditis (AP) cases. We sought to compare the prevalence and severity of objective findings seen in patients with RP. A retrospective single-center study during 2010-2019, including 765 patients diagnosed with AP. Clinical, electrocardiographic, echocardiographic, and laboratory findings were extracted from the local electronic health records. Recurrence during follow-up was documented in 134 patients (17.5%), with a median time to recurrence of 101 (± 59-251) days. The median age was 60 years (IQR 45-72), 68% were male. Most patients were defined as having idiopathic\viral pericarditis (64%). The clinical manifestation during the recurrent event of pericarditis was less prominent or attenuated when compared to the initial event-ECG signs (ST elevation 12% vs. 26%; p = 0.006, Knuckle sign 13% vs. 33%; p < 0.001, ST larger in lead L2 than L3 4% vs. 19%; p < 0.001), pericardial effusion moderate and above (11% vs. 30%; p = 0.02), and inflammatory markers (mean peak CRP levels 66 mg/l vs. 97 mg/l; p < 0.001). Similar results were seen in the subgroup of patients defined as having idiopathic\viral pericarditis. Up to 20% of patients who did not have ECG signs or a significant pericardial effusion in their 1st event demonstrated these findings during the recurrence, though still to a lesser extent compared with those who had these signs in their 1st event. The objective findings of AP are less pronounced during recurrent events. Future studies should focus on the role of advanced biomarkers and imaging in defining true RP events.

Modifiers of the Association between E/e' Ratio and Survival among Patients with No Apparent Structural or Functional Cardiac Abnormality.

BACKGROUND: The ratio between early mitral flow wave to early diastolic mitral annulus velocity (E/e' ratio) varies according to age and sex and is associated with mortality in heart failure. We sought to describe the association between E/e' and mortality in patients with no apparent structural or functional cardiac abnormality and explore possible modifiers of this association. METHODS: A retrospective study of 104,315 patients who underwent echocardiographic evaluation during 2009-2021 in the largest tertiary center in Israel. Patients with cancer, ventricular dysfunction, significant valvular or structural heart disease, or evidence of pulmonary hypertension were excluded. RESULTS: The final analysis included 32,836 patients with a median age of 56 (43-66) years, and 13,547 (41%) were female. The median E/e' was 8.3 (6.8-10.3), and 9,306 (28%) had an E/e' >10. During a median follow-up of 5.7 (3.3-8.5) years, 2,396 (7.3%) individuals died. E/e' >10 was associated with mortality (adjusted hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.07-1.27, p<0.001). The mortality risk associated with E/e' >10 was significantly higher in those aged ≤70 (HR 1.26, 95% CI 1.12-1.42, p<0.001), males (HR 1.34, 95% CI 1.19-1.49, p<0.001), a normal left ventricular mass (HR 1.13, 95% CI 1.02-1.24, p = 0.017), and pulmonary artery pressure <30 mmHg (HR 1.18, 95% CI 1.06-1.30, p = 0.003). CONCLUSION: An elevated E/e' is associated with mortality, specifically in younger individuals, males, and those with a normal left ventricular mass and lower pulmonary artery pressure. This suggests that an elevated E/e' might be a marker of subclinical risk in these subgroups. Further studies are needed to identify whether an elevated E/e' is useful in shared decision-making regarding the management of cardiovascular risk factors.

Absence of Pericarditis Recurrence in Rilonacept-Treated Patients With COVID-19 and SARS-CoV-2 Vaccination: Results From the RHAPSODY Long-term Extension.

Background: Rilonacept inhibits the interleukin-1 pathway, and extended treatment in patients with recurrent pericarditis (RP) reduced recurrence risk by 98% in the phase 3 trial, RHAPSODY long-term extension (LTE). Severe acute respiratory syndrome (SARS)-CoV-2 vaccination and/or infection may trigger pericarditis recurrence, and in clinical practice, it is unknown whether to continue rilonacept during SARS-CoV-2 infection. This post-hoc analysis of the RHAPSODY LTE aimed to inform rilonacept management in RP patients vaccinated against SARS-CoV-2 or who contract COVID-19. Methods: Analysis was conducted from May 2020 to June 2022. The LTE portion of RHAPSODY LTE enabled up to 24 months of additional open-label rilonacept treatment beyond the pivotal study. Rilonacept efficacy data in preventing pericarditis recurrence were assessed, and concomitant SARS-CoV-2 vaccination and COVID-19 adverse event data were evaluated. Results: No pericarditis recurrences were temporally associated with vaccination. Sixteen COVID-19 cases were reported; 10 in 30 unvaccinated or partially vaccinated patients (33%) vs 6 of 44 fully vaccinated patients (14%; P = 0.04). Twelve of 16 patients (75%) were receiving rilonacept at the time of infection, and none experienced pericarditis recurrence. One pericarditis recurrence occurred in the peri-COVID-19 period in 1 of 4 patients who had stopped rilonacept treatment > 4.5 months prior. COVID-19 severity was mild in 13 patients, moderate in 2, and severe in 1. Conclusions: Full vaccination effectively reduced COVID-19 events in patients treated with rilonacept. Vaccination or COVID-19 during rilonacept treatment did not increase pericarditis recurrence. Continued rilonacept treatment in patients contracting COVID-19 did not worsen disease severity, whereas rilonacept interruption increased pericarditis recurrence, supporting a recommendation for continued rilonacept treatment for RP during vaccination or COVID-19. ClinicalTrialsgov identifier: NCT03737110.

Contexte: Le rilonacept inhibe la voie de l'interleukine-1 et, d'après les résultats de la période de prolongation à long terme de l'essai de phase III RHAPSODY, la poursuite du traitement par cet agent chez les patients atteints de péricardite récidivante a réduit le risque de récidive de 98 %. La vaccination contre le syndrome respiratoire aigu sévère (SRAS)-CoV-2 ou l'infection à ce virus pourrait toutefois déclencher une récidive de la péricardite, et dans la pratique clinique, on ignore s'il vaut mieux poursuivre le traitement par rilonacept pendant l'infection à SRAS-CoV-2. Cette analyse post-hoc de la période de prolongation à long terme de l'essai RHAPSODY vise à orienter la gestion du rilonacept chez les patients atteints de péricardite récidivante qui sont vaccinés contre le SRAS-CoV-2 ou qui contractent la COVID-19. Méthodologie: L'analyse a été effectuée de mai 2020 à juin 2022. La période de prolongation à long terme de l'essai RHAPSODY a permis d'accumuler des données en mode ouvert pendant une période allant jusqu'à 24 mois au-delà de l'étude pivot. Les données sur l'efficacité du rilonacept en prévention de la récidive de péricardite ont été évaluées, tout comme les données sur la vaccination concomitante contre le SRAS-CoV-2 et les cas de COVID-19. Résultats: Aucune récidive de la péricardite n'a pu être associée sur le plan temporel avec la vaccination. Au total, 16 cas de COVID-19 ont été signalés, dont 10 chez les patients non vaccinés ou partiellement vaccinés sur 30 (33 %) et 6 chez les patients complètement vaccinés sur 44 (14 %; p = 0,04). De ces 16 patients, 12 (75 %) prenaient du rilonacept au moment de l'infection et aucun n'a connu de récidive de la péricardite. Une récidive de la péricardite s'est produite dans la période suivant la COVID-19 chez 1 des 4 patients qui avaient cessé de prendre le rilonacept > 4,5 mois auparavant. La COVID-19 a été légère chez 13 patients, modérée chez 2 patients et sévère chez 1 patient. Conclusions: La vaccination complète a réduit efficacement les cas de COVID-19 chez les patients traités par le rilonacept. La vaccination ou l'infection à SRAS-CoV-2 pendant le traitement par rilonacept n'a pas augmenté le risque de récidive de la péricardite. La poursuite du traitement par rilonacept chez les patients atteints de COVID-19 n'a pas aggravé la sévérité de la maladie, tandis que l'interruption du traitement a augmenté le risque de récidive de la péricardite, ce qui plaide en faveur de la recommandation de poursuivre le traitement de la péricardite récidivante par le rilonacept pendant la vaccination ou la COVID-19. Numéro d'identification ClinicalTrialsgov: NCT03737110.

Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept.

BACKGROUND: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment. METHODS AND RESULTS: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001). CONCLUSIONS: In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

Ventricular arrhythmias in patients with hypertrophic cardiomyopathy: Prevalence, distribution, predictors, and outcome.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden cardiac death. Ventricular fibrillation (VF) is thought to be the common culprit arrhythmia. OBJECTIVE: The purpose of this study was to describe the incidence and predictors of sustained ventricular arrhythmias (VTAs) in HCM patients. METHODS: We retrospectively analyzed all patients with HCM and an implantable cardioverter-defibrillator (ICD) from a prospectively derived registry in 2 tertiary medical centers. Clinical, electrocardiographic, echocardiographic, ICD interrogation, and genetic data were collected and compared, first between patients with and without VTAs and then between patients with only VF and those with ventricular tachycardia (VT) with or without VF. RESULTS: Of the 1328 HCM patients, 207 (145 [70%] male; mean age 33 ± 16 years) were implanted with ICDs. Over a mean follow-up of 10 ± 6 years, 37 patients with ICDs (18%) developed sustained VTAs. These were associated with a family history of sudden cardiac death and a personal history of VTAs (P = .036 and P = .001, respectively). Sustained monomorphic VT was the most common arrhythmia (n = 26, 70%) and was linked to decreased left ventricular (LV) ejection fraction and increased LV end-systolic and end-diastolic diameters. Antitachycardia pacing (ATP) successfully terminated 258 (79%) of the 326 VT events. Mortality rates were comparable between patients with and without VTAs (4 [11%] vs 29 [17%]; P = .42) and between those with and without ICDs (24 [16%] vs 85 [20%]; P = .367). CONCLUSION: VT rather than VF is the most common arrhythmia in patients with HCM; it is amenable to ATP and is associated with lower LV ejection fraction and higher LV diameters. Therefore, ATP-capable devices may be considered in HCM patients with these LV features.

Ser77Tyr transthyretin amyloidosis in Israel: Initial manifestations and diagnostic features.

OBJECTIVE: Amyloidosis due to the transthyretin Ser77Tyr mutation (ATTRS77Y) is a rare autosomal-dominant disorder, characterized by carpal-tunnel syndrome, poly- and autonomic-neuropathy, and cardiomyopathy. However, related symptoms and signs are often nonspecific and confirmatory tests are required. We describe the age and frequency of early symptoms and diagnostic features among individuals of Jewish Yemenite descent in Israel. METHODS: Records of mutation carriers were retrospectively reviewed. ATTRS77Y diagnosis was defined by the presence of amyloid in tissue and/or amyloid-related cardiomyopathy. RESULTS: We identified the Ser77Tyr mutation at the heterozygous state in 19 amyloidosis patients (mean age at diagnosis: 62 ± 5.7 years, range 49-70) and 30 amyloid-negative carriers. The probability for disease diagnosis increased from 4.4% at age 49 to 100% at 70 and occurred earlier in males. Initial symptoms preceded diagnosis by 5 ± 3.8 years (range 0-12) and were commonly sensory changes in the extremities. Erectile dysfunction predated these in 8/13 (62%) males. In two patients cardiac preceded neurological symptoms. Two patients declined symptoms. Electrophysiological studies near the time of diagnosis indicated a median neuropathy at the wrist in 18/19 (95%) and polyneuropathy in 13/19 (68%). Skin biopsy revealed epidermal denervation in 15/16 (94%) patients. Cardiomyopathy was identified in 16/19 (84%). Sensory complaints or epidermal denervations were present in 17/30 (57%) of amyloid-negative carriers and co-occurred in 10/30 (33%). INTERPRETATION: ATTRS77Y symptoms commonly occur after age 50, but may begin earlier. Median neuropathy, skin denervation and cardiomyopathy are frequently identified. Symptoms may be absent in patients and common in amyloid-negative carriers.

The clinical course of patients with previous acute and recurrent pericarditis receiving the BNT162b2 vaccine.

Background: Vaccines against SARS-COV2 have been crucial in efforts against COVID19, yet there have been reports of pericarditis following vaccination with mRNA-based vaccines. Methods: We questioned consecutive patients with a history of acute pericarditis (AP) evaluated in the pericardial disease clinic during 3-11/2020 in a single tertiary center. Patients with significant myocardial involvement or pericarditis secondary to another systemic disease were excluded. Results: We included 64 patients in the final analysis. Mean age was 53.1 (±18), and 26 (41%) were female. At least 1 recurrence of AP was documented in 47 (73%) cases, 32 (50%) had ≥ 3 recurrences prior to vaccination. AP was considered to be idiopathic\viral in 45 (70%) cases, 20 (31%) cases were post-injury. All patients received at least 2 doses of the vaccine, and 48 patients (75%) received a 3rd dose. Two cases of breakthrough COVID19 infections were documented. Overall, 12 patients (19%) reported any adverse events. Of which, 2 had recurrent pericarditis. There was a trend for a younger age in those patients who had adverse events (median age 45 [IQR 36-61] vs. 60 [38-71], p = 0.08). no other significant difference was seen. Conclusion: In patients with a history of acute\recurrent pericarditis, the use of BNT162b2 was mostly uneventful, but some mild disease recurrences did occur.

Characterization of heart failure patients with reverse left ventricular remodelling post-angiotensin receptor blockers/neprilysin inhibitors therapy.

AIMS: To assess the effect of angiotensin receptor blockers/neprilysin inhibitors (ARNI) on left ventricular (LV) ejection fraction (LVEF) and LV dimensions in a real-life cohort of heart failure and reduced ejection fraction (HFrEF) patients, while analysing patient characteristics that may predict reverse LV remodelling. METHODS AND RESULTS: The ARNI-treated HFrEF patients followed at a single tertiary medical centre HF-outpatient clinic were included in the study. Clinical and echocardiographic parameters were evaluated prior to ARNI initiation, and while on ARNI therapy, assessing patient characteristics associated with reverse LV remodelling. The cohort included 91 patients (mean age 60.5 years, 90% male) and 47 (52%) patients exhibited ARNI responsiveness, defined as an increase in LVEF during therapy. Overall, LVEF increased by 19% post-ARNI (23.8 to 28.4%, P < 0.001). Subgroup analysis revealed several parameters associated with significant LVEF improvement, including baseline LVEF <30%, non-ischaemic HF aetiology, lack of cardiac resynchronization therapy (CRT), better initial functional class and ARNI initiation within 3 years from HF diagnosis (P ≤ 0.001 for all). Significant reduction in LV dimensions was noted in patients with lower initial LVEF, non-ischaemic HF and no CRT. Further combined subgrouping of the study population demonstrated that patients with both LVEF <30% and a non-ischaemic HF gained most benefit from ARNI with an average of 51% improvement in LVEF (19.9 to 30%, P < 0.001). CONCLUSIONS: The ARNI treatment response is not uniform among HFrEF patient subgroups. More pronounce reverse LV remodelling is associated with early ARNI treatment initiation in the course of HFrEF, and in those with LVEF <30%, non-ischaemic HF and no CRT.

Hypokinetic hypertrophic cardiomyopathy: clinical phenotype, genetics, and prognosis.

AIMS: To describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes. METHODS AND RESULTS: Our registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing-risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all-cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1-10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF. CONCLUSIONS: Hypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.

Influence of anesthesia on hemodynamic assessment of mitral stenosis severity.

BACKGROUND: The treatment of choice for severe rheumatic mitral stenosis (MS) is balloon mitral valvuloplasty (BMV). Assessment of MS severity is usually performed by echocardiography. Before performing BMV, invasive hemodynamic assessment is also performed. The effect of anesthesia on the invasive assessment of MS severity has not been studied. The purpose of the present study was to assess changes in invasive hemodynamic measurement of MS severity before and after induction of general anesthesia. METHODS: The medical files of 22 patients who underwent BMV between 2014 and 2020 were reviewed. Medical history, laboratory, echocardiographic and invasive measurements were collected. Anesthesia induction was performed with etomidate or propofol. Pre-procedural echocardiographic measurements of valve area using pressure half time, and continuity correlated well with invasive measurements using the Gorlin formula. RESULTS: After induction of anesthesia the mean mitral valve gradient dropped by 2.4 mmHg (p = 0.153) and calculated mitral valve area (MVA) increased by 0.2 cm2 (p = 0.011). A wide variability in individual response was observed. While a drop in gradient was noted in 14 patients, it increased in 7. Gorlin derived MVA rose in most patients but dropped in 4. Assuming a calculated MVA of 1.5 cm2 and below to define clinically significant MS, 4 patients with pre-induction MVA of 1.5 cm2 or below had calculated MVA above 1.5 cm2 after induction. CONCLUSIONS: The impact of general anesthesia on the hemodynamic assessment of MS is heterogeneous and may lead to misclassification of MS severity.