COVID-19 and Patients with Heart Failure

Angiotenzin konvertirajući enzim 2 (ACE2) je protein koji služi kao ulazno mjesto SARS-CoV-2 u stanice ljudskog organizma. Strukturno je sličan angiotenzin konvertirajućem enzimu, ali u usporedbi s njim ima antagonističku ulogu u renin-angiotenzin-aldosteronskom sustavu, te drugačiju ciljnu molekulu. ACE2 protein prisutan je u raznim tkivima u ljudi, uključujući epitel pluća i miokard. Trenutna saznanja upućuju da su srčane manifestacije COVID-19 prvenstveno povezane sa zahvaćenošću krvnih žila u SARS-CoV-2 infekciji. Zatajivanje srca opisivano je u bolesnika s COVID-19 od samog početka pandemije, s učestalosti od oko 25 %. Iako trenutno nema dovoljno podataka vezano za tip zatajivanja srca u COVID-19 bolesnika, trenutno dostupni podaci upućuju na češću pojavnost zatajivanja srca sa smanjenom ejekcijskom frakcijom. Zbog uloge ACE2 proteina u renin-angiotenzin-aldosteronskom sustavu, nameće se pitanje učinka lijekova koji inhibiraju navedeni sustav (inhibitori angiotenzin konvertirajućeg enzima i blokatori receptora za angiotenzin II) u pogledu susceptibilnosti bolesnika liječenih navedenim lijekovima na obolijevanje od SARS-CoV-2, kao i pitanje izazivanja težega kliničkog tijeka bolesti. S druge strane, valja uzeti u obzir opasnosti ukidanja lijekova iz ove skupine u bolesnika sa zatajivanjem srca. Prema dosadašnjim spoznajama, uporaba ovih lijekova ne povećava sklonost zarazi SARS-CoV-2 niti je povezana sa značajnim porastom rizika razvoja teškoga ili smrtonosnoga kliničkog tijeka COVID-19 te se nastavak liječenja ovim skupinama lijekova preporučuje od strane vodećih kardioloških društava.Angiotensin-converting enzyme 2 (ACE2) is a protein which serves as the entry point for SARS-CoV-2 into human cells. Although structurally similar to angiotensin-converting enzyme, it serves an antagonistic purpose in the renin-angiotensin-aldosterone system (RAAS), and has a different target molecule. The ACE2 protein is present in various human tissues, including the lung epithelium and myocardium. It is currently thought that cardiac manifestations of COVID-19 are primarily linked to vascular involvement in SARS-CoV-2 infection. Heart failure has been described in COVID-19 patients since the start of the pandemic, with a frequency of around 25%. Although at present there is insufficient data regarding the type of heart failure in COVID-19 patients, current available data suggests a more common occurrence of heart failure with reduced ejection fraction. Due to the role of the ACE2 protein in the RAAS, questions have arisen regarding the effect of medications that inhibit the aforementioned system (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers), on the susceptibility of patients treated with the said drugs to SARS-CoV-2 infection, as well as on the development of a more severe clinical course of the disease. Conversely, it is important to consider the dangers of discontinuing medications from this group of drugs in patients with heart failure. According to current insights, the use of these drugs does not increase susceptibility to SARS-CoV-2 infection, nor are they associated with an increased risk of developing a more severe or fatal clinical course of COVID-19; thus, continuation of therapy is recommended by leading cardiac societies

COVID-19 and Patients with Heart Failure

Angiotenzin konvertirajući enzim 2 (ACE2) je protein koji služi kao ulazno mjesto SARS-CoV-2 u stanice ljudskog organizma. Strukturno je sličan angiotenzin konvertirajućem enzimu, ali u usporedbi s njim ima antagonističku ulogu u renin-angiotenzin-aldosteronskom sustavu, te drugačiju ciljnu molekulu. ACE2 protein prisutan je u raznim tkivima u ljudi, uključujući epitel pluća i miokard. Trenutna saznanja upućuju da su srčane manifestacije COVID-19 prvenstveno povezane sa zahvaćenošću krvnih žila u SARS-CoV-2 infekciji. Zatajivanje srca opisivano je u bolesnika s COVID-19 od samog početka pandemije, s učestalosti od oko 25 %. Iako trenutno nema dovoljno podataka vezano za tip zatajivanja srca u COVID-19 bolesnika, trenutno dostupni podaci upućuju na češću pojavnost zatajivanja srca sa smanjenom ejekcijskom frakcijom. Zbog uloge ACE2 proteina u renin-angiotenzin-aldosteronskom sustavu, nameće se pitanje učinka lijekova koji inhibiraju navedeni sustav (inhibitori angiotenzin konvertirajućeg enzima i blokatori receptora za angiotenzin II) u pogledu susceptibilnosti bolesnika liječenih navedenim lijekovima na obolijevanje od SARS-CoV-2, kao i pitanje izazivanja težega kliničkog tijeka bolesti. S druge strane, valja uzeti u obzir opasnosti ukidanja lijekova iz ove skupine u bolesnika sa zatajivanjem srca. Prema dosadašnjim spoznajama, uporaba ovih lijekova ne povećava sklonost zarazi SARS-CoV-2 niti je povezana sa značajnim porastom rizika razvoja teškoga ili smrtonosnoga kliničkog tijeka COVID-19 te se nastavak liječenja ovim skupinama lijekova preporučuje od strane vodećih kardioloških društava.Angiotensin-converting enzyme 2 (ACE2) is a protein which serves as the entry point for SARS-CoV-2 into human cells. Although structurally similar to angiotensin-converting enzyme, it serves an antagonistic purpose in the renin-angiotensin-aldosterone system (RAAS), and has a different target molecule. The ACE2 protein is present in various human tissues, including the lung epithelium and myocardium. It is currently thought that cardiac manifestations of COVID-19 are primarily linked to vascular involvement in SARS-CoV-2 infection. Heart failure has been described in COVID-19 patients since the start of the pandemic, with a frequency of around 25%. Although at present there is insufficient data regarding the type of heart failure in COVID-19 patients, current available data suggests a more common occurrence of heart failure with reduced ejection fraction. Due to the role of the ACE2 protein in the RAAS, questions have arisen regarding the effect of medications that inhibit the aforementioned system (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers), on the susceptibility of patients treated with the said drugs to SARS-CoV-2 infection, as well as on the development of a more severe clinical course of the disease. Conversely, it is important to consider the dangers of discontinuing medications from this group of drugs in patients with heart failure. According to current insights, the use of these drugs does not increase susceptibility to SARS-CoV-2 infection, nor are they associated with an increased risk of developing a more severe or fatal clinical course of COVID-19; thus, continuation of therapy is recommended by leading cardiac societies

Heart transplantation in patient with diabetes- related microvacular and macrovascular complications

Cardiac transplantation is a method of choice in the treatment of patients with end-stage heart failure (HF) whose life expectancy, despite the optimal medical therapy is less than one year. Number of patiences with diabetes are increasing at alarming rates. Some studies have shown an increased risk of post-transplant infection, transplanted organ rejection, renal failure and mortality in diabetic recipients. A 38-year-old African American male patient with end-stage ischemic biventricular cardiomyopathy and diabetes mellitus type 1 with moderate chronic renal failure, was transplanted in August 2014. A few days following the transplantation his renal function continued to deteriorate and chronic haemodialysis was initiated. During the next four years, the regular heart biopsies showed no signs of acute cellular or humoral rejection and echocardiography showed normal graft function. In February 2018 the patient was listed for kidney transplantation. In April 2018 the patient presented with septic shock. Due to the severe eosinophilia combined with culture-negative severe sepsis, complete viral and parasitic serology was performed. All tests came back negative. Bone marrow aspiration showed only eosinophilia. Due to the sepsis of unknown origin, the patient was treated with broad-spectrum antibiotic therapy without an effective response to applied therapy. Despite of the all intensive care treatment, the patient died. Autopsy showed a pancarditis possibly caused by Trypanosoma cruzi or Toxoplasma gondii. In conclusion, cardiac transplantation can be performed in diabetic patients with chronic renal failure, but with significantly increased risk for further renal deterioration and even the need for chronic haemodialysis

Validation of the new classification criteria for systemic lupus erythematosus on a patient cohort from a national referral center: a retrospective study

AIM: To validate Systemic Lupus International Collaborating Clinics (SLICC)-12 and American College of Rheumatology (ACR)-97 classification criteria on a patient cohort from the University Hospital Center Zagreb. ----- METHODS: This retrospective study, conducted from 2014 to 2016, involved 308 patients with systemic lupus erythematosus (SLE) (n=146) and SLE-allied conditions (n=162). Patients' medical charts were evaluated by an expert rheumatologist to confirm the clinical diagnosis, regardless of the number of the ACR-97 criteria met. Overall sensitivity and specificity, as well as the sensitivity and specificity according to disease duration, were compared between ACR-97 and SLICC-12 classifications. Predictive value for SLE for both classifications was assessed using logistic regression and receiver operating characteristic (ROC) curves. ----- RESULTS: The SLICC-12 criteria had significantly higher sensitivity in early disease, which increased with disease duration. The ACR-97 criteria had higher specificity. The specificity of the SLICC-12 criteria was low and decreased with disease duration. Regression analysis demonstrated the superiority of the SLICC-12 classification criteria over the ACR-97 criteria, with areas under the ROC curve of 0.801 and 0.780, respectively. ----- CONCLUSION: Although the SLICC-12 criteria were superior to the ACR-97 and were more sensitive for diagnosing early SLE, their specificity in our population was too low. The sensitivity of the SLICC-12 classification is increased by better defined clinical features within each criterion. Our results contribute to the current initiative for developing new criteria for SLE

Post-transplant lymphoproliferative disorder after heart transplantation

Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid neoplasms associated with immunosuppression following solid organ transplantation or allogeneic hematopoietic stem cell transplantation. Mismatch for cytomegalovirus (CMV), such as when a seronegative recipient receives an organ from a seropositive donor, was shown to be associated with a seven-fold increase in PTLD. A 20-year-old male patient was admitted to the hospital due to back and abdominal pain. He had underwent a heart transplant 6 years ago due to postmyocarditic dilated cardiomyopathy and soon after the transplant, he had developed CMV pneumonitis. At examination, abdominal ultrasound showed multiple lesions of the liver, and patohystology of the lesion biopsy revealed PTLD, i.e. Non-Hodgkin’s diffuse large B cell lymphoma, for which the patient received 8 cycles of chemotherapy (R-CHOP protocol). Nine months after the first dose, the patient was admitted to the hospital due to simptoms of heart failure (NYHA IV) and echocardiography revealed significantly reduced cardiac function (LVEF 25%). Graft rejection was excluded with heart biopsy and it was concluded the etiology of heart failure was anthracycline (Doxorubicin) toxicity. Given the severity of the patient’s condition, he was again listed for heart transplant, and ultimately, retransplanted. Eight years after the retransplant, the patient is in excellent overall condition. Heart transplant patients have about a 1- 6% risk to develop the PTLD. The incidence of chronic Doxorubicin cardiotoxicity is about 1.7%. This patient had developed both, but, fortunately, with timely and right therapy the outcome can be successful

Heart transplantation in patient with diabetes- related microvacular and macrovascular complications

Cardiac transplantation is a method of choice in the treatment of patients with end-stage heart failure (HF) whose life expectancy, despite the optimal medical therapy is less than one year. Number of patiences with diabetes are increasing at alarming rates. Some studies have shown an increased risk of post-transplant infection, transplanted organ rejection, renal failure and mortality in diabetic recipients. A 38-year-old African American male patient with end-stage ischemic biventricular cardiomyopathy and diabetes mellitus type 1 with moderate chronic renal failure, was transplanted in August 2014. A few days following the transplantation his renal function continued to deteriorate and chronic haemodialysis was initiated. During the next four years, the regular heart biopsies showed no signs of acute cellular or humoral rejection and echocardiography showed normal graft function. In February 2018 the patient was listed for kidney transplantation. In April 2018 the patient presented with septic shock. Due to the severe eosinophilia combined with culture-negative severe sepsis, complete viral and parasitic serology was performed. All tests came back negative. Bone marrow aspiration showed only eosinophilia. Due to the sepsis of unknown origin, the patient was treated with broad-spectrum antibiotic therapy without an effective response to applied therapy. Despite of the all intensive care treatment, the patient died. Autopsy showed a pancarditis possibly caused by Trypanosoma cruzi or Toxoplasma gondii. In conclusion, cardiac transplantation can be performed in diabetic patients with chronic renal failure, but with significantly increased risk for further renal deterioration and even the need for chronic haemodialysis

Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis

Development of cardiac allograft vasculopathy represents the major determinant of long-term survival in patients after heart transplantation. Due to graft denervation, these patients seldom present with classic symptoms of angina pectoris, and the first clinical presentations are progressive heart failure or sudden cardiac death. Although coronary angiography remains the routine technique for coronary artery disease detection, it is not sensitive enough for screening purposes. This is especially the case in the first year after transplantation when diffuse and concentric vascular changes can be easily detected only by intravascular ultrasound. The treatment of the established vasculopathy is disappointing, so the primary effort should be directed toward early prevention and diagnosis. Due to diffuse vascular changes, revascularization procedures are restricted only to a relatively small proportion of patients with favorable coronary anatomy. Percutaneous coronary intervention is preferred over surgical revascularization since it leads to better acute results and patient survival. Although there is no proven long-term advantage of drug-eluting stents for the treatment of in-stent restenosis, they are preferred over bare-metal stents. Severe vasculopathy has a poor prognosis and the only definitive treatment is retransplantation. This article reviews the present knowledge on the pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft vasculopathy